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The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well‐established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89‐year‐old female, diagnosed with epidermal growth factor receptor (EGFR)‐mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis. [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood. Methods: Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase‐like 3 (METTL3), and insulin‐like growth factor‐2 mRNA‐binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)‐qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay. Results: BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR‐treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A‐IGF2BP3‐dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo. Conclusion: BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3‐mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The VELOUR randomized phase III trial established aflibercept (an anti-angiogenic targeting VEGF-A, VEGF-B, and placenta growth factor) combined with FOLFIRI as an effective treatment in patients with metastatic colorectal cancer (mCRC) failing a prior oxaliplatin-based regimen. This real-world study mandated by Polish Health Authorities aimed at assessing the benefits/risks of aflibercept plus FOLFIRI prescribed to Polish patients with mCRC according to reimbursement criteria. The activity of aflibercept plus FOLFIRI in such patients was confirmed, and no new safety signal was reported. Background: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. Methods: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints. Results: A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9–9.9] and 27.0 months [95% CI, 23.9–30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%). Conclusions: The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed. [ABSTRACT FROM AUTHOR]

Introduction: It is well known that patients with objective response to pembrolizumab have a durable duration of response, leading to favorable survival outcomes. We investigated the possibility of predicting the objective response with concise indicators obtained from daily clinical practice. Methods: In our multi-institutional cohort, 220 platinum-refractory metastatic urothelial carcinoma (mUC) patients treated with pembrolizumab for at least 6 weeks with complete information of objective response were investigated. Results: The median follow-up was 7.3 months, and 119 patients deceased during the follow-up. A multivariate logistic regression analysis exhibited two independent variables predicting the objective response, including the neutrophil-lymphocyte ratio (NLR) change at 6 weeks of treatment and liver metastasis. We proposed a risk group using these two indicators. Patients with no predictive indicators/one of those were assigned to favorable (42%)/intermittent (47%) risk groups. Patients with both indicators were assigned to poor risk (11%). Notably, the objective response rate was well delineated in 41%, 25%, and 0% for favorable-, intermediate-, and poor-risk groups, respectively (p < 0.001). Distinct overall survival (OS) between the risk groups was also confirmed with the median OS of 14.1, 11.7, and 4.2 months in favorable-, intermediate-, and poor-risk groups, respectively. Conclusions: At the 6 weeks of the pembrolizumab treatment, our risk model predicts the objective response rate precisely. Notably, those classified as "poor risk" – marked by liver metastasis and an increased NLR – should be considered for alternative therapy with a different mode of action, highlighting a critical decision point in treatment optimization. [ABSTRACT FROM AUTHOR]

Introduction: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] vs. GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. Methods: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n = 183, 74%; GCS, n = 91; GC, n = 92). Results: The tumor shrinkage pattern could be divided into 4 categories based on the response at 100 days after enrollment: categories A (<–30% in size), B (−30–0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], p < 0.0001). Each category predicted the best response and overall survival (p < 0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was −53% in the GCS arm and −65% in the GC arm (p = 0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. Conclusion: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed regrowth after 6 cycles. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. Following sorafenib, lenvatinib (LENV) has been approved as a first‐line treatment option for unresectable HCC. In the past few years, at least 9 large‐scale cohort studies have examined the efficacy and safety of LENV compared to atezolizumab plus bevacizumab (ATE/BEV) in unresectable HCC, but there is currently no direct meta‐analysis conducted for a comprehensive consolidation. To provide the most updated meta‐analysis of the clinical efficacy and safety of ATE/BEV versus LENV for patients with unresectable HCC. Our studies comparing the efficacy and safety of ATE/BEV and LENV in unresectable HCC were systematically searched in PubMed, Embase, and Web of Science from inception to February 2023. Outcomes measured were overall survival (OS), progression‐free survival (PFS), mortality, complete response (CR), partial response (PR), objective response rate (ORR), disease control rate (DCR), progressive disease (PD), stable disease (SD), and adverse events (AEs). Seven eligible studies involving 4428 patients (1569 in the ATE/BEV group and 2859 in the LENV group) were included in the narrative synthesis. All baseline characteristics were similar between the 2 groups except for Child‐Pugh class B. Ultimately, our meta‐analysis showed that the LENV group had longer OS and PFS than the ATE/BEV group. Moreover, patients on LENV were more likely to achieve SD, whereas those on ATE/BEV were more likely to achieve PR. [ABSTRACT FROM AUTHOR]

Abnormal activation of the Wnt/β-catenin signaling pathway is a driving force behind the progression of gastric cancer. Atovaquone, known as an antimalarial drug, has emerged as a potential candidate for anti-cancer therapy. This study investigated atovaquone's effects on gastric cancer and its underlying mechanisms. Using gastric cancer cell lines, we found that atovaquone, at concentrations relevant to clinical use, significantly reduced their viability. Notably, atovaquone exhibited a lower effectiveness in reducing the viability of normal gastric cells compared to gastric cancer cells. We further demonstrated that atovaquone inhibited gastric cancer growth and colony formation. Mechanism studies revealed that atovaquone inhibited mitochondrial respiration and induced oxidative stress. Experiments using ρ0 cells, deficient in mitochondrial respiration, indicated a slightly weaker effect of atovaquone on inducing apoptosis compared to wildtype cells. Atovaquone increased phosphorylated β-catenin at Ser45 and Ser33/37/Thr41, elevated Axin, and reduced β-catenin. The inhibitory effects of atovaquone on β-catenin were reversed upon depletion of CK1α. Furthermore, the combination of atovaquone with paclitaxel suppressed gastric cancer growth and improved overall survival in mice. Given that atovaquone is already approved for clinical use, these findings suggest its potential as a valuable addition to the drug arsenal available for treating gastric cancer. [ABSTRACT FROM AUTHOR]

Kinase is an enzyme that helps in the phosphorylation of the targeted molecules and can affect their ability to react with other molecules. So, kinase influences metabolic reactions like cell signaling, secretory processes, transport of molecules, etc. The increased activity of certain kinases may cause various types of cancer, i.e. leukemia, glioblastoma, and neuroblastomas. So, the growth of particular cancer cells can be prevented by the inhibition of the kinase responsible for those cancers. Natural products are the key resources for the development of new drugs where approximately 60% of anti-tumor drugs are being developed with the same including specific kinase dwellers. This study comprised molecular interactions of various molecules (obtained from natural sources) as kinase inhibitors for the treatment of cancer. It is expected that by analyzing the skeleton behavior, the process of action, and the body-related activity of these organic products, new cancer-avoiding molecules can be developed. [ABSTRACT FROM AUTHOR]

Introduction: Platinum-based chemotherapy is the mainstay of first-line therapy for advanced-stage non-small cell lung cancer (NSCLC). Although carboplatin-induced hypersensitivity reactions (HSRs) commonly occur following multiple cycles of therapy, they are rarely observed during the first cycle of the treatment. Case report: Here, we report the case of a 70-year-old man with advanced-stage NSCLC who developed HSR possibly caused by carboplatin during the first cycle of induction with platinum-doublet chemotherapy plus pembrolizumab. The patient presented with bronchial obstruction due to a centrally located tumor. No driver mutations were detected, and the programmed death-ligand 1 expression ranged from 1% to 24%. Consequently, the patient was treated with pembrolizumab combined with carboplatin and paclitaxel. However, immediately after the start of carboplatin, the blood pressure and oxygen levels of the patient dropped and he began exhibiting an altered level of consciousness. These findings indicated carboplatin-induced anaphylaxis. Hypotension and oxygen desaturation improved following carboplatin discontinuation and normal saline administration. Management and outcome: The basophil activation test for both carboplatin and cisplatin was negative. Thus, the risk of anaphylaxis owing to both drugs was ruled out, and carboplatin was believed to have induced grade 3 HSR. Subsequently, carboplatin-based chemotherapy was switched to cisplatin-based chemotherapy. HSR was not observed during the four treatment cycles with pembrolizumab, cisplatin, and pemetrexed, and best response was partial response. Discussion: Cisplatin-based chemotherapy could be used as an alternate treatment in patients with NSCLC who develop severe carboplatin-induced HSR. [ABSTRACT FROM AUTHOR]

Objective: Patients with cancer often use complementary and alternative medication (CAM). This research aims to study the current attitude of healthcare professionals toward the use of CAM to improve current care. Methods: A questionnaire on both the current practice and opinions about CAM use was sent to healthcare professionals in Amsterdam UMC, who work for the department of hematology or oncology. Oncologists, hematologists, residents, (specialized) nurses, dieticians, (hospital)pharmacists, and pharmacy technicians were asked to participate in this study. Results: Among eligible healthcare professionals, 77 responded to the questionnaire (34%). Overall, 87% of healthcare professionals indicate it is important to be aware of their patient's CAM use, and all find the potential of drug–herb interactions important. However, more than half of the healthcare professionals inquire about the patient's CAM use infrequently. In addition, only 15% of the healthcare professionals stated they had sufficient knowledge of CAM to advise patients on their use of CAM. Conclusions: Healthcare professionals are aware of the potential risks of CAM use in combination with anti-cancer treatment. However, CAM use is not yet discussed with every patient. This may be due to healthcare professionals' lack of knowledge about CAM. [ABSTRACT FROM AUTHOR]

Background: There have been reports on the impact of concurrent drugs on the outcome of immunotherapy for non‐small cell lung carcinoma (NSCLC). However, the effect of some drugs, such as antibiotics and nonsteroidal anti‐inflammatory drugs (NSAIDs), has not been clarified in patients with NSCLC. In the present study, we aimed to assess the association between concurrent drugs and the outcomes of immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy for patients with advanced NSCLC. Methods: We retrospectively assessed patients with advanced NSCLC who underwent ICI treatment between September 2017 and December 2021 at Kobe University Hospital. We evaluated the data regarding the use of antibiotics within 30 days before ICI initiation, as well as the use of proton pump inhibitors (PPIs) and NSAIDs during ICI initiation. Results: A total of 127 patients were assessed, among whom 28 (22.0%) patients received antibiotics, 39 (30.7%) PPIs, and 36 (28.3%) NSAIDs. No significant differences were observed between the patients with and without antibiotic use. However, patients using NSAIDs had significantly worse objective response rates (ORR) and progression‐free survival (PFS) with ICI alone or in combination with chemotherapy compared to those who did not (ORR, 47.2% vs. 67.0%; p = 0.045. PFS, 6.3 months vs. 10.8 months; p = 0.02). Patients using PPIs demonstrated a worse ORR of ICI in combination with chemotherapy compared to those who did not (ORR, 45.2% vs. 72.6%; p = 0.013). Conclusions: The unnecessary use of NSAIDs along with immunotherapy should be discouraged. [ABSTRACT FROM AUTHOR]

Background: For advanced non‐small cell lung cancer (NSCLC), combination therapies including a PD‐1 inhibitor plus chemotherapy or a PD‐1 inhibitor, CTLA‐4 inhibitor, and chemotherapy are standard first‐line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real‐world setting. Methods: In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first‐line therapies in 182 patients with stage IIIB–IV NSCLC. Primary outcomes were overall survival (OS) and progression‐free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan–Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD‐L1 expression. Results: In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3–4 adverse events occurred comparably, but immune‐related adverse events were numerically more frequent in the CNI group. Conclusions: In real‐world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. Methods: A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. Results: Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P =.7), social eating (P =.8), xerostomia (P =.9)]. Conclusion: In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function. [ABSTRACT FROM AUTHOR]

Purpose Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by providing periodic updates on new and anticipated novel drug approvals. Summary Selected drug approvals anticipated in the 12-month period covering the first quarter of 2024 through the fourth quarter of 2024 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics, as selected from 59 novel drugs awaiting US Food and Drug Administration approval. This year's pipeline includes recently added drugs with various indications including oncology, infectious diseases, genetic disorders, and rare diseases. New cellular and gene therapies are rapidly evolving and being studied for several rare diseases and cancers. Conclusion More oncology agents, including gene therapies, oral agents, and monoclonal antibodies, are in the pipeline this year. Additional diseases targeted by new novel drugs, including cellular and gene therapies, are hemophilia, nonalcoholic steatohepatitis, Alzheimer's disease, and rare diseases such as galactosemia and epidermolysis bullosa. [ABSTRACT FROM AUTHOR]

Introduction: Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high‐quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non‐small cell lung cancer (NSCLC) protocols in China, on the risk–benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. Methods: To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross‐dimensional real‐world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit–risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. Discussion: This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Discussed here is a review of the changing landscape in the treatment of mantle cell lymphoma (MCL) regarding the emergence and use of targeted therapy. Targeted therapy is the use of small molecules designed to interrupt specific mechanisms within the cancer cell to exert anti-tumor efficacy. Targeting such mechanisms relies upon our understanding of what makes a cancer cell malignant. MCL is a difficult-to-treat lymphoid cancer that relies heavily upon constitutive intracellular signaling, promoting its growth and survival. The mainstay of MCL treatment has been to treat it with cytotoxic chemotherapy; however, targeted therapies have allowed for improved treatment outcomes and continue to change the way we manage this disease. This review aims to describe what targeted therapies are being utilized in MCL treatment and their mechanisms of action, safety, and efficacy, as well as future directions for their use in MCL treatment. Mantle cell lymphoma (MCL) is a rare, heterogeneous B-cell non-Hodgkin's lymphoma. The standard front-line treatment utilizes chemotherapy, often followed by consolidation with an autologous hematopoietic cell transplant; however, in most patients, the lymphoma will recur and require subsequent treatments. Additionally, mantle cell lymphoma primarily affects older patients and is frequently chemotherapy-resistant, which has further fostered the necessity for new, chemotherapy-free treatment options. In the past decade, targeted therapies in mantle cell lymphoma have been practice-changing as the treatment paradigm shifts further away from relying primarily on cytotoxic agents. Here, we will review the pathophysiology of mantle cell lymphoma and discuss the emergence of targeted, chemotherapy-free treatments aimed at disrupting the abnormal biology driving its lymphomagenesis. Treatments targeting the constitutive activation of NF-kB, Bruton's Tyrosine Kinase signaling, and anti-apoptosis will be the primary focus as we discuss their clinical data and toxicities. Our review will also focus primarily on the emergence and use of targeted therapies in the relapsed/refractory setting but will also discuss the emergence of their use in front-line therapy and in combination with other agents. [ABSTRACT FROM AUTHOR]

Simple Summary: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has been successfully used as a conditioning regimen in acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. In this study, we investigated how increased doses of melphalan impact the safety of HDCT with TreoMel and patient outcomes. A total of 51 AML patients were included in the analysis: 31 (60.8%) received standard-dose treosulfan combined with melphalan 140 mg/m2 (TreoMel 140) and 20 (39.2%) received melphalan 200 mg/m2 (TreoMel 200). There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohorts. The side effect profile was comparable between both patient groups. Our results show that a higher melphalan dose is well tolerated. No significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and short follow-up. Longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. (1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients' basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is predicted to be the second-highest cause of cancer mortality in the US by 2040. It is driven by various mutations including KRAS, TP53, SMAD4, and CDKN2A. Roughly 1 in 10 patients with pancreatic cancer have wildtype KRAS (KRASWT). We studied 27 patients with KRASWT to better understand their molecular characteristics and potential for precision medicine. Our findings revealed that KRASWT PDAC is enriched with potentially treatable genetic alterations, including those affecting the MAPK pathway, DNA repair pathway, and kinase fusion genes. One of our KRASWT PDAC patients was found to have a specific, targetable TFG-MET mutation and they responded well to treatment with a cMET inhibitor. This suggests that KRASWT PDAC has unique genetic characteristics that could be targeted with specific treatments tailored to each patient, highlighting the importance of comprehensive genetic profiling in KRASWT PDAC. Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: Low-grade serous ovarian cancer is a rare type of ovarian cancer that usually has an indolent growth and affects younger women. It has markers that suggest it might respond to hormone therapy, but unfortunately, this treatment does not work well for many patients because the cancer becomes resistant to it. We do not fully understand why this happens. In breast cancer, similar resistance mechanisms are studied, so we are exploring if we can apply what we learn there to improve treatment for this type of ovarian cancer. This review looks at why hormone therapy might stop working in ovarian cancer and explores new ways to make it more effective. The goal is to find better treatment options for patients with advanced low-grade serous ovarian cancer, who currently do not have many choices for treatment. Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due to the development of endocrine resistance. The mechanisms of resistance, whether primary or acquired, are still largely unknown and present a significant hurdle in achieving favorable treatment outcomes with endocrine therapy in these patients. In estrogen receptor-positive breast cancer, mechanisms of endocrine resistance have been largely explored and novel treatment strategies to overcome resistance have emerged. Considering the shared estrogen receptor positivity in LGSOC and breast cancer, we wanted to explore whether there are any parallel mechanisms of resistance and whether we can extend endocrine breast cancer treatments to LGSOC. This review aims to highlight the underlying molecular mechanisms possibly driving endocrine resistance in ovarian cancer, while also exploring the available therapeutic opportunities to overcome this resistance. By unraveling the potential pathways involved and examining emerging strategies, this review explores valuable insights for advancing treatment options and improving patient outcomes in LGSOC, which has limited therapeutic options available. [ABSTRACT FROM AUTHOR]

Simple Summary: The mainstay of treatment for non-muscle invasive bladder cancer is transurethral resection of the tumor followed by intravesical treatment for intermediate- or high-risk disease. Duration and type of intravesical treatment depend on specific characteristics of the tumor and the patient's disease course. Patients with non-muscle invasive bladder cancer are closely monitored with frequent surveillance cystoscopies following treatment. This type of cancer has a low progression rate; however, it has a high rate of recurrence with the current recommended treatments. Therefore, patients often find themselves having to undergo multiple resections and rounds of intravesical treatment throughout their lifetime. This is not only burdensome for patients but also costly for the healthcare system. Given the high recurrence with the standard treatment options, it is important to continue investigating novel therapies. The goal of this review article is to outline the most recent therapies available or in clinical trials for the treatment of non-muscle invasive bladder cancer. The landscape of treatment for non-muscle invasive bladder cancer is rapidly changing. A complete and careful transurethral resection is the mainstay of initial treatment and is followed by intravesical therapy in intermediate or high-risk cases. The standard of care is intravesical BCG. Many alternative or additive approaches to this are being explored. We divided this review into three relevant spaces to consider these novel treatment approaches: (1) low-risk disease, for which intravesical therapy is not usually considered, (2) BCG-naïve disease (i.e., considering alternatives to the standard therapy), and (3) BCG-unresponsive disease. We performed a review of published literature and summarized ongoing trials in the United States. Novel approaches that we explored include surgical techniques for resection, alterations in dwell time for intravesical therapy, delivery method and schedule of intravesical therapies, new intravesical therapy agents, and systemic therapies (especially immunotherapy). These are thoroughly outlined throughout this review article, and the numerous modalities being studied demonstrate significant promise for the future treatment of the expanding space of NMIBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Classical Hodgkin Lymphoma is a blood cancer, accounting for 0.5% of all new cancer diagnoses. Despite high cure chances, approximately 20% of patients are refractory to frontline treatment or relapse thereafter. Treatment strategies for relapsed/refractory patients have progressively lower chances of inducing a persistent complete remission. Therefore, great efforts are being made to further improve rates of response of frontline therapy, as well as to explore the efficacy of new compounds and different drug combinations. The present review aims to summarize these efforts, offering an overview of recent advances and future perspectives in the field. Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients' T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular directed therapy for hepatocellular carcinoma (HCC) involves targeting specific signaling pathways that normally promote cancer cell growth and survival. Accordingly, a blockage of these pathways leads to tumor shrinkage and improves the patient outcome. Recent advancements in molecular directed therapies have focused on tyrosine kinase and angiogenesis inhibition, thus targeting pathways involved in the molecular pathogenesis of HCC. Especially the vascular endothelial growth factor (VEGF) signaling pathway is one of the most prominent pathways involved in HCC progression. The combination of inhibiting VEGF signaling and immune-directed therapy or double immunocheckpoint inhibition are the mainstay of contemporary treatment strategies and promising agents for future combination treatment regimens. However, the effectiveness of these therapies may vary among patients, highlighting the need to identify the specific molecular alterations for tailored therapeutic approaches. Additionally, in modern systemic therapy of patients with HCC, the underlying pathology of the liver has always been encountered to identify population subgroups in terms of pathophysiology and underlying liver function to predict response to different therapeutic regimens. We conducted a comprehensive review of the current literature of published data and clinical trials (MEDLINE), as well as published congress contributions and active recruiting clinical trials on targeted therapies in hepatocellular carcinoma. Combinations of different agents and medical therapy along with radiological interventions were analyzed for the setting of advanced HCC. Those settings were also analyzed in combination with adjuvant situations after resection or radiological treatments. We summarized the current knowledge for each therapeutic setting and combination that currently is or has been under clinical evaluation. We further discuss the results in the background of current treatment guidelines. In addition, we review the pathophysiological mechanisms and pathways for each of these investigated targets and drugs to further elucidate the molecular background and underlying mechanisms of action. Established and recommended targeted treatment options that already exist for patients are considered for systemic treatment: atezolizumab/bevacizumab, durvalumab/tremelimumab, sorafenib, lenvatinib, cabozantinib, regorafenib, and ramucirumab. Combination treatment for systemic treatment and local ablative treatment or transarterial chemoembolization and adjuvant and neoadjuvant treatment strategies are under clinical investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Selecting and developing effective therapies for distinct epithelial ovarian cancer subtypes necessitates tumor models that accurately recapitulate the individual characteristics and microenvironmental interactions. Patient-derived tumor models offer a promising approach by preserving the tumor's integrity, providing a platform for personalized treatment strategies. Zebrafish embryos could be a useful tool for quickly testing potential treatments in parallel. In this research article, we aimed to evaluate the model using a real-world case study and compare results with existing in vitro and in vivo models. A patient-derived cell line from a low-grade serous ovarian cancer with a KRAS mutation was engrafted in zebrafish embryos. Xenografts were assigned to a five-day treatment with trametinib and/or luminespib, targeting two complementary pathways that have previously shown efficacy in other cancer models of this cell line. The zebrafish model offers several options to analyze the response of the tumor to drug exposure. Here, we evaluated both cell growth and cell death, which showed a significant positive tumor response upon treatment that was amplified further by combining the drugs. Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines and 3D tumor models. To address this goal, a well-characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G>T (p.(Gly12Val)) was used. Fluorescently labeled tumor cells were injected into the perivitelline space of 2 days' post-fertilization zebrafish embryos. At 1 day post-injection, xenografts were assessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib and trametinib + luminespib. Subsequently, xenografts were euthanized and analyzed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC. [ABSTRACT FROM AUTHOR]

Introduction: Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. Methods: Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jka) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fyb and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. Results: Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. Discussion: Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment. [ABSTRACT FROM AUTHOR]

Coactivator-associated arginine methyltransferase 1 (CARM1) is significant as a key member of the PRMT family, crucial for regulating arginine methylation, and its association with colorectal cancer underscores its potential as a therapeutic target. Consequently, CARM1 inhibitors have emerged as potential therapeutic agents in cancer treatment and valuable chemical tools for cancer research. Despite steady progress in CARM1 inhibitor research, challenges persist in discovering effective, isoform-selective, cell-permeable, and in vivo-active CARM1 inhibitors for colorectal cancer. This review summarizes the research progress on CARM1 and its relationship with colorectal cancer, aiming to provide a theoretical basis for the radiotherapy of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Malignant glomus tumors (MGTs) are rare malignancies, which grow rapidly and are aggressive. Surgical resection has been regarded as the standard management, but treatment options for those unresectable tumors are limited, resulting in a high recurrence rate and poor prognosis. Case Description: An 85-year-old man presented with gross hematuria and was diagnosed with MGTs of bladder. The patient achieved long-term local control after multimodal therapy comprising radiotherapy, iodine-125 seeds brachytherapy, transcatheter arterial chemoembolization, and antiangiogenic targeted therapy. Conclusion: MGTs occurring in the bladder are clinically rare and refractory. The case presented here highlights the importance of multidisciplinary diagnosis and treatment, providing evidence that radiotherapy and antiangiogenic therapy may play an important role in unresectable bladder MGT. [ABSTRACT FROM AUTHOR]

Aims: This study sets out to identify dysregulated plexins and investigate their roles in KIRC through an integrated bioinformatics approach. Methods: RNA-sequencing data and clinicopathological information of KIRC, extracted from The Cancer Genome Atlas (TCGA) database, were used to perform comprehensive bioinformatics analysis. Results: Almost all plexin gene family members were dysregulated in KIRC. Univariate and multivariate Cox regression analyses revealed that PLXNA1/B3 were independent prognostic factors of overall survival in patients with KIRC. Mechanically, PLXNA1/B3 may promote ccRCC progression through several cancer-related signaling pathways, tumor immunity, and angiogenesis. Drug sensitivity analysis suggested that vemurafenib was the potential drug for PLXNA1/B3. Conclusion: Herein, we found that PLXNA1/B3 were independent prognostic factors, making them attractive new targets for KIRC treatment. [ABSTRACT FROM AUTHOR]

Introduction: Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations. Methods: We conducted a retrospective cohort study of patients with HR+, HER2− MBC treated with alpelisib and ET. We assessed the safety, tolerability, and effectiveness of alpelisib in a real-world population. Deidentified patient-, tumor-, and outcome-related data, including AEs, were collected and summarized. Kaplan-Meier methods were applied for survival analyses, and stratified analyses of interest were conducted. A p value <0.05 was considered statistically significant. Results: A total of 76 women treated with alpelisib + ET were included in our cohort. Most had been previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The estimated median progression-free survival was 5.2 months (95% CI, 4.1–8.0). The median overall survival was longer among patients without prior everolimus therapy (hazard ratio, 4.28 [95% CI, 1.64–11.16]; p = 0.0012), and no significant outcome differences were observed between patients treated with different starting doses of alpelisib. Approximately 31.6% of patients permanently discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea (10.5%). Conclusions: For progressive HR+, HER2− MBC, alpelisib + ET showed effectiveness in a real-world patient population that was comparable to published clinical trial data, regardless of starting dose. However, the effectiveness of alpelisib following previous everolimus exposure may be limited and, hence, should be a consideration to decide sequencing of therapy in these patients. Patients treated with alpelisib are at risk for clinically relevant AEs and require close monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Neuroendocrine carcinoma (NEC) is characterized by a poor prognosis and is generally treated with platinum and etoposide combination therapy as first-line chemotherapy. However, it remains uncertain whether carboplatin and etoposide combination therapy (CE) and cisplatin and etoposide combination therapy (PE) have comparable treatment efficacy. In this retrospective analysis, we compared the efficacy and safety of CE and PE in patients with NEC. Methods: We retrospectively reviewed the patient's clinical record from 2005 to 2022 at the Department of Medical Oncology, Tohoku University Hospital. Patients who received either CE or PE were included in the study. Statistical analyses were performed using JMP Pro 16.0 (SAS Institute Inc., Cary, NC, USA). Results: A total of 104 patients were enrolled, with 73 patients assigned to the CE group and 31 patients assigned to the PE group. Statistically, the response rate, progression-free survival time and overall survival time were 42.6%, 5.1 months (95% CI: 3.5–6.3) and 13.6 months (95% CI: 8.9–17.4), respectively, in the CE groups and 44.4%, 5.6 months (95% CI: 3.1–7.0) and 12.5 months (95% CI: 11.2–14.6), respectively, in the PE groups. There was no significant difference in treatment efficacy between the CE and the PE groups. However, the number of patients with elevated creatinine (3.35 mg/dL and 3.88 mg/dL in 2 patients, respectively) was significantly higher in the PE group than in the CE group. Conclusion: The efficacy of CE and PE in patients with NEC is comparable. However, the incidence of renal dysfunction was found to be significantly higher in the PE group than in the CE group. [ABSTRACT FROM AUTHOR]

Background: Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods: We searched all the relevant studies in PubMed, Embase, and Cochrane Library databases. We also reviewed abstracts of relevant conferences to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results: CRT combined with immunotherapy can improve progression-free survival (PFS) (hazard rate [HR]: 0.60, 95% confidence interval [CI, 0.55–0.60) and overall survival (OS) (HR: 0.59, 95% CI, 0.53–0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5–52.7%) and 71.3% (95% CI, 67.3–75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95% CI, 51.0–70.3%) and 77.4% (95% CI, 73.2–81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95% CI, 31.3–39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95% CI, 31.9–51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95% CI, 5.0–8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95% CI, 3.1–6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95% CI, 2.9–7.3%). Conclusions: Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real‐world study and a meta‐analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. Methods: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1‐, 2‐, and 3‐year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1‐year recurrence rate, R0 resection rate and adverse events. Moreover, a meta‐analysis of 27 published literatures was also conducted for comparison. Results: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1‐, 2‐, and 3‐year OS rates were 91.41% (95% CI: 85.15%–95.63%), 75.00% (95% CI: 66.58%–82.23%) and 64.84% (95% CI: 55.91%–73.07%).ORR and DCR were 31.2% (95% CI: 23.31–39.99) and 64.1% (95% CI: 55.15%–72.38%), and the 1‐year recurrence rate was 26.7% (95% CI: 22.5%–38.1%). Treatment‐related events occurred in 96.1% but were acceptable. In a meta‐analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1‐year recurrence rate of 12%. Conclusion: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed. [ABSTRACT FROM AUTHOR]

Background: Patients with HER2-positive cancers often face a poor prognosis, and treatment regimens containing anti-HER2 have become the first-line treatment options for breast and gastric cancers. However, these approaches are faced with significant challenges in terms of drug resistance. Hence, it is crucial to explore precise treatment strategies aimed at improving survival outcomes. Advancements in treatment: Over the past few years, there has been rapid advancement in the realm of tumor therapy, particularly with the swift progress of immune checkpoint inhibitors, including PD-1/PD-L1 inhibitors. They exert anti-tumor effects by disrupting immune-suppressive factors within the tumor microenvironment. However, monotherapy with PD-1/PD-L1 inhibitors has several limitations. Consequently, numerous studies have explored combinatorial immunotherapeutic strategies and demonstrated highly promising avenues of development. Objective: This article aims to review the clinical trials investigating PD-1/PD-L1 inhibitor combination therapy for HER2-positive tumors. Additionally, it provides a summary of ongoing trials evaluating the efficacy and safety of these combined treatments, with the intention of furnishing valuable insights for the clinical management of HER2-positive cancer. Conclusion: Combinatorial immunotherapeutic strategies involving PD-1/PD-L1 inhibitors hold considerable promise in the treatment of HER2-positive tumors. Continued research efforts and clinical trials are warranted to elucidate optimal treatment regimens that maximize therapeutic benefits while minimizing adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients' hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX. [ABSTRACT FROM AUTHOR]

Background: Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents. Methods: PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models. Results: Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35–65%) for low-grade gliomas (LGG) and 40% (95% CI: 29–51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36–54%) for both glioma grades. The complete response rate was 13% (95% CI: 05–27%) for HGG and 5% (95% CI: 1–10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58–98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34–79%). Grade 1–4 adverse events occurred in 100% of LGG and 63% of HGG patients. Conclusions: Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma patients with high neutrophil counts often show impaired clinical response and poor prognosis, indicating that neutrophils can support melanoma progression. The precise mechanism responsible for this correlation, especially in the context of targeted therapy, still requires clarification. We show that peripheral blood neutrophils of patients with advanced melanoma are characterized by lower CD16 surface expression compared to healthy donors, which has been reported to be associated with tumor promotion. We provide evidence that melanoma cells under dual-targeted therapy can be protected in vitro by neutrophils from both patients and healthy donors. In addition, this protective effect is dependent on cell–cell contact, as well as on culture conditions, and is observed under nonadherence. Unraveling the mechanism, the interference with the protease activity of neutrophils reduced protection. Understanding the complex interaction of neutrophils and melanoma cells might aid in discovering methods to prevent the tumor-promoting effects by neutrophils in patients. Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell–cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the effectiveness of the targeted cancer medication CDK4/6 inhibitors, in patients with breast cancer. These medicaments have been used for nearly a decade, but how well they work can vary greatly from one patient to another. By examining the experiences of 86 patients over a period from November 2016 to May 2020, we aimed to understand what factors might predict better or worse outcomes for patients. We discovered that certain characteristics, like the level of the progesterone receptor in the tumor and whether the cancer had spread to multiple locations or the liver, played a significant role in how long patients benefited from treatment without progression. The study also found that management characteristics during treatment could significantly affect patient outcomes. These insights are crucial for developing personalized management strategies that could lead to better outcomes for people with breast cancer. Background: The quest to comprehend the real-world efficacy of CDK4/6 inhibitors (CDKis) in breast cancer continues, as patient responses vary significantly. Methods: This single-center retrospective study evaluated CDKi use outside the trial condition from November 2016 to May 2020. Progression-free survival (PFS), time-to-treatment failure (TTF), short-term and prolonged treatment benefit (≥4 and ≥10 months), as well as prognostic and predictive markers were assessed with Kaplan–Meier and multivariate regression analyses. Results: Out of 86 identified patients, 58 (67.4%) had treatment failure of which 40 (46.5%) were due to progression. Median PFS and TTF were 12 and 8.5 months, respectively. A total of 57 (66.3%) and 42 (48.8%) patients experienced short-term and prolonged treatment benefit. Independent, significant predictors for PFS were progesterone receptor expression (HR: 0.88), multiple metastatic sites (HR: 2.56), and hepatic metastasis (HR: 2.01). Significant predictors for TTF were PR expression (HR: 0.86), multiple sites (HR: 3.29), adverse events (HR: 2.35), and diabetes (HR: 2.88). Aside from tumor biology and adverse events, treatment modifications like pausing and switching of CDKi were predictive for short-term (OR: 6.73) and prolonged (OR: 14.27) therapeutic benefit, respectively. Conclusions: These findings emphasize the importance of tailored treatment strategies, highlighting the role of PR expression, metastatic burden, and therapeutic adjustments in optimizing patient outcomes in real-world breast cancer management. [ABSTRACT FROM AUTHOR]

Simple Summary: Although women 70 years of age and older represent a large percentage of newly diagnosed breast cancer cases, older individuals are drastically underrepresented in clinical trials. Most women diagnosed with breast cancer at 70 years of age and older present with hormone receptor-positive (HR+) breast cancer. Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapy has become the standard of care for metastatic HR+ breast cancer. This study reports that metastatic breast cancer patients ≥70 years of age receiving CDK4/6 inhibitor-based treatment, particularly when combined with an aromatase inhibitor, experience prolonged progression-free survival but display no such prolongation in overall survival and report more frequent adverse effects to treatment. The reported findings can aid in the development of optimized treatments based on age and help older patients weigh treatment options. The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320 patients with metastatic breast cancer receiving CDK4/6 inhibitor combined with fulvestrant or an aromatase inhibitor were enrolled in an ongoing observational study or were included in an IRB-approved retrospective study. All patients receiving CDK4/6 inhibitor-based therapy that were ≥70 years of age (n = 111) displayed prolonged progression-free survival (27.6 months) as compared to patients <70 years of age (n = 209, 21.1 months, HR = 1.38, p < 0.05). Specifically, patients receiving a CDK4/6 inhibitor with an aromatase inhibitor who were ≥70 years of age (n = 79) displayed exceptionally prolonged progression-free survival (46.0 months) as compared to patients receiving the same treatment who were <70 years of age (n = 161, 21.8 months, HR = 1.71, p < 0.01). However, patients ≥70 years of age also experienced more frequent adverse responses to CDK4/6 inhibitor-based treatment leading to dose reduction, hold, or discontinuation than the younger cohort (69% and 53%, respectively). Treatment strategies that may decrease toxicity without affecting efficacy (such as dose titration) are worth further exploration. [ABSTRACT FROM AUTHOR]

Simple Summary: Human epidermal receptor (HER) 2-positive advanced gastric cancer (AGC) is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. After the success of a ToGA trial, the development of treatment for HER2-positive AGC had been at a standstill for a long time. Recently, trastuzumab deruxtecan in later-line therapy and the combination therapy of chemotherapy plus trastuzumab with immune checkpoint inhibitor has demonstrated significant survival benefit in first-line treatment. Currently, several clinical trials of new types of anti-HER2 agents are ongoing. Human epidermal receptor (HER) 2-positive advanced gastric cancer is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. Although combination therapy with trastuzumab and chemotherapy provides meaningful survival benefit, clinical trials targeting HER2 have failed to demonstrate clinical benefits in first- or subsequent-line treatment. Trastuzumab deruxtecan, an antibody–drug conjugate, has shown positive results even in later-line treatment and has become new standard treatment. In first-line therapy, combination therapy with pembrolizumab and trastuzumab plus chemotherapy demonstrated a dramatic response rate. Therefore, the FDA rapidly approved it without waiting for the results of survival time. The emergence of combination therapy including immunotherapy with HER2-targeting agents and the development of HER2 targeting agents with or without immunotherapy have been advancing for treating HER2-positive gastric cancer. In this review, we will discuss the current status of treatment development and future perspectives for HER2-positive gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroblastoma (NB) presents with two patterns of disease: with or without metastasis. Both types of disease presentation include tumors with high-risk (HR) features. The management of HR-NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 immunotherapy. Anti-GD2 monoclonal antibodies (mAbs) have significantly improved the outcome of HR-NB patients but they are mostly effective against disease affecting the bone and/or bone marrow (known as the osteomedullary compartment), and less so against soft tissue disease. The question arises as to whether anti-GD2 immunotherapy might benefit HR-NB patients with disease compounded by only soft tissue. In this retrospective review, we found that achieving first complete remission with chemotherapy, surgery, and radiotherapy does not prevent the risk of relapse. However, adding anti-GD2 mAbs once the patient has achieved complete remission significantly decreases the chances of relapse by 80%. Our study provides further support to indicate anti-GD2 mAbs in all cases with HR-NB. Neuroblastoma presents with two patterns of disease: locoregional or systemic. The poor prognostic risk factors of locoregional neuroblastoma (LR-NB) include age, MYCN or MDM2-CDK4 amplification, 11q, histology, diploidy with ALK or TERT mutations, and ATRX aberrations. Anti-GD2 immunotherapy has significantly improved the outcome of high-risk (HR) NB and is mostly effective against osteomedullary minimal residual disease (MRD), but less so against soft tissue disease. The question is whether adding anti-GD2 monoclonal antibodies (mAbs) benefits patients with HR-NB compounded by only soft tissue. We reviewed 31 patients treated at SJD for HR-NB with no osteomedullary involvement at diagnosis. All tumors had molecular genetic features of HR-NB. The outcome after first-line treatment showed 25 (80.6%) patients achieving CR. Thirteen patients remain in continued CR, median follow-up 3.9 years. We analyzed whether adding anti-GD2 immunotherapy to first-line treatment had any prognostic significance. The EFS analysis using Cox models showed a HR of 0.20, p = 0.0054, and an 80% decrease in the risk of relapse in patients treated with anti-GD2 immunotherapy in the first line. Neither EFS nor OS were significantly different by CR status after first-line treatment. In conclusion, adding treatment with anti-GD2 mAbs at the stage of MRD helps prevent relapse that unequivocally portends poor survival. [ABSTRACT FROM AUTHOR]

Simple Summary: In solid tumors, oxygen concentration varies between different regions. Generally, while oxygen supply is sufficient in the vicinity of blood vessels, the concentration of oxygen gradually drops as the distance from the blood vessel increases. In the regions with low oxygen content (hypoxic regions), cancer cells acquire various malignant properties, like invasiveness, altered metabolism, and therapy resistance, leading to recurrence and poor clinical outcomes of patients. Hypoxia-inducible factor (HIF) is a major regulator of hypoxia responses. Herein, we summarized how tumor hypoxia activates different mechanisms, in both HIF-dependent and HIF-independent manners, and contributes to the acquisition of chemotherapy resistance. We also discussed the involvement of epigenetic regulation in hypoxia-induced chemoresistance, with a specific example of ATAD2 protein degradation inducing drug resistance under hypoxia. Finally, we briefly reviewed some current clinical trials that target HIF and tumor hypoxia for cancer treatment or therapy sensitization. In hypoxic regions of malignant solid tumors, cancer cells acquire resistance to conventional therapies, such as chemotherapy and radiotherapy, causing poor prognosis in patients with cancer. It is widely recognized that some of the key genes behind this are hypoxia-inducible transcription factors, e.g., hypoxia-inducible factor 1 (HIF-1). Since HIF-1 activity is suppressed by two representative 2-oxoglutarate-dependent dioxygenases (2-OGDDs), PHDs (prolyl-4-hydroxylases), and FIH-1 (factor inhibiting hypoxia-inducible factor 1), the inactivation of 2-OGDD has been associated with cancer therapy resistance by the activation of HIF-1. Recent studies have also revealed the importance of hypoxia-responsive mechanisms independent of HIF-1 and its isoforms (collectively, HIFs). In this article, we collate the accumulated knowledge of HIF-1-dependent and independent mechanisms responsible for resistance of hypoxic cancer cells to anticancer drugs and briefly discuss the interplay between hypoxia responses, like EMT and UPR, and chemoresistance. In addition, we introduce a novel HIF-independent mechanism, which is epigenetically mediated by an acetylated histone reader protein, ATAD2, which we recently clarified. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of atezolizumab and bevacizumab is a standard treatment for unresectable hepatocellular carcinoma. This study investigated the relationship between the gut microbiome and treatment efficacy. Fecal samples from 37 patients with hepatocellular carcinoma treated with this combination were analyzed. Patients were divided into responders (n = 28) and non-responders (n = 9). While overall microbiome diversity was similar, certain bacteria, such as Bacteroides stercoris and Parabacteroides merdae were more abundant in responders. Patients lacking these bacteria had worse prognoses. This suggests that differences in gut microbiota play a role in the effectiveness of atezolizumab and bevacizumab therapy. The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder (n = 28) and non-responder (n = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of Bacteroides stercoris and Parabacteroides merdae was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab. [ABSTRACT FROM AUTHOR]

Simple Summary: Use of cancer biomarkers for tumor aggressiveness is an unmet clinical need. Differentiation of high-risk versus low-risk tumors may guide physicians to select appropriate treatment strategies tailored to the risk level of individual patients. This study aimed to evaluate the value of an optical redox imaging technique for differentiating a human melanoma mouse xenograft model with a high risk of metastasis from a low-risk mouse model. Several imaging indices were found to be significantly different between the two models. The high-risk model was found to be in a more oxidized status and to have a higher intratumor redox heterogeneity. These findings may inform further research development of the optical redox imaging approach into translatable cancer biomarkers in the future. To develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp. Here, we implemented a calibration procedure to facilitate imaging the nominal concentrations of tissue NADH and Fp in the mouse xenografts of two human melanoma lines, an indolent less metastatic A375P and a more metastatic C8161. Images of the redox indices (NADH, Fp, ORR) revealed the existence of more oxidized areas (OAs) and more reduced areas (RAs) within individual tumors. ORR was found to be higher and NADH lower in C8161 compared to that of A375P xenografts, both globally for the whole tumors and locally in OAs. The ORR in the OA can differentiate xenografts with a higher statistical significance than the global averaged ORR. H&E staining of the tumors indicated that the redox differences we identified were more likely due to intrinsically different cell metabolism, rather than variations in cell density. [ABSTRACT FROM AUTHOR]

Simple Summary: Sacituzumab govitecan is an antibody–drug conjugate that has been approved for the treatment of metastatic triple-negative breast cancer and, recently, also for metastatic hormone receptor-positive HER2-negative breast cancer. Although patients with metastatic breast cancer frequently need palliative radiotherapy, none of the published prospective trials studied the combination of radiotherapy and Sacituzumab govitecan. We conducted a multi-center retrospective cohort study to assess the efficacy and safety of Sacituzumab govitecan and palliative radiotherapy. We did not find signs of increased toxicity, and response rates were favorable despite extensive prior treatment. More research is necessary to determine the optimal integration of novel systemic agents and radiotherapy in the palliative setting. Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody–drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration. [ABSTRACT FROM AUTHOR]

Background. Janus-activated kinase 2 (JAK2) plays a pivotal role in numerous essential biological processes, including proliferation, apoptosis, and metastasis in human cells. Prior studies have indicated that inhibiting JAK2 could be a promising strategy to mitigate cell proliferation and induce apoptosis in tumor cells. Objectives. This study aimed to estimate the binding affinity of 79 herbal compounds, comprising 46 flavonoids, 21 anthraquinones, and 12 cinnamic acids, to the ATP-binding cleft of JAK2 to identify potential herbal inhibitors of JAK2. Methods. The binding affinities between ligands and JAK2 were calculated utilizing AutoDock 4.0 software in conjunction with the Cygwin environment. Cross-validation was conducted using the Schrödinger tool. Molecular dynamics simulations were employed to evaluate the stability of docked poses for the most significant JAK2 inhibitors. Furthermore, the Discovery Studio Visualizer tool was utilized to elucidate interactions between the top-ranked JAK2 inhibitors and residues within the JAK2 ATP-binding site. Results. Twelve flavonoids, two anthraquinones, and three cinnamic acids demonstrated substantial binding affinities to the protein kinase domain of the receptor, with a criterion of Δ G binding < −10 kcal/mol. Among the studied flavonoids, anthraquinones, and cinnamic acid derivatives, orientin, chlorogenic acid, and pulmatin emerged as the most potent JAK2 inhibitors, exhibiting Δ G binding scores of −14.49, −11.87, and −10.76 kcal/mol, respectively. Furthermore, the docked poses of orientin, pulmatin, and chlorogenic acid remained stable throughout 60 ns computer simulations. The average root mean square deviation values calculated for JAK2 when complexed with orientin, chlorogenic acid, and pulmatin were 2.04 Å, 2.06 Å, and 1.95 Å, respectively. Conclusion. This study underscores the robust inhibitory potential of orientin, pulmatin, and chlorogenic acid against JAK2. The findings hold promise for the development of novel and effective drugs for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed (PEM) is the primary chemotherapy for non‐small cell lung cancer (NSCLC), showing potential for long‐term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. Methods: A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. Results: Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor‐1 (TTF‐1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001). Conclusions: Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF‐1 positivity, could enhance disease control rates and extend survival. [ABSTRACT FROM AUTHOR]

The article provides information on Toripalimab-tpzi, a programmed death receptor-1 (PD-1)-blocking antibody, an antineoplastic agent. Toripalimab-tpzi is used in combination with cisplatin and gemcitabine for first-lien treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC). Also mentioned are its dosage and administration, drug interactions, and advice to patients.

We present a patient with lung adenocarcinoma showing high PD‐L1 expression and BRAF V600E mutation, who achieved a remarkable long‐term response to the combination therapy of dabrafenib and trametinib (DT treatment) after disease progression on immunotherapy. This case may provide an opportunity for clinicians to consider the order of administration of immunotherapy and molecular targeted therapy for BRAF V600E‐positive lung cancer. [ABSTRACT FROM AUTHOR]

Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-HL patients in China. Nineteen cases of HIV-HL were diagnosed and treated at three center and including the sixth people's hospital of Zhengzhou, Peking union medical college hospital, and Chongqing university cancer hospital, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed. The median age at diagnosis was 43(22–74) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man having sex with man (MSM) and nine cases transmitted through heterosexual transmission. Seven patients were diagnosed with lymphoma and found to be infected with HIV. Four cases were in stage III, and fifteen cases were in stage IV. After a median follow up of 46.8(4.0-112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with combination antiretroviral therapy (cART). The 5-year progression-free survival (PFS) and overall survival (OS) rate were 83.9% and 89.5%,respectively. HIV-HL exhibits an invasive process in clinical practice, and cART combined with ABVD regimen chemotherapy can achieve long-term survival for patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a comprehensive overview of the approved chimeric antigen receptor T-cell products (CAR T-cells), their specific indications, treatment-related side effects, and scientific challenges. CAR T-cells have been introduced to modern hematology over the last years and have changed treatment outcomes in heavily pretreated patients with B-cell and plasma cell malignancies. To date, six commercially available CAR T-cell products have been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA). These advanced therapeutic medicinal products induce strong treatment effects but can also cause adverse events that can potentially be life-threatening. Therefore, a thorough understanding of CAR T-cell function and characteristics is essential for safety and efficacy. This review provides a comprehensive overview of the clinical applications of CAR T-cells, focusing on the approved products and emphasizing their benefits but also indicating limitations and challenges. Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, and many patients have benefited from its use. To date, six CAR T-cell products have been approved by the FDA and EMA, and many more are being developed and investigated in clinical trials. The whole field of adoptive cell transfer has experienced an unbelievable development process, and we are now at the edge of a new era of immune therapies that will have its impact beyond hematologic malignancies. Areas of interest are, e.g., solid oncology, autoimmune diseases, infectious diseases, and others. Although much has been achieved so far, there is still a huge effort needed to overcome significant challenges and difficulties. We are witnessing a rapid expansion of knowledge, induced by new biomedical technologies and CAR designs. The era of CAR T-cell therapy has just begun, and new products will widen the therapeutic landscape in the future. This review provides a comprehensive overview of the clinical applications of CAR T-cells, focusing on the approved products and emphasizing their benefits but also indicating limitations and challenges. [ABSTRACT FROM AUTHOR]