Search

Background: Targeted agents were introduced over past years because of better understanding of oncogenetic mechanisms in metastatic renal cell carcinoma (mRCC). These agents include tyrosine kinase inhibitors (TKIs) such as sorafenib, sunitinib, pazopanib and axitinib.

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

Based on its absence in normal tissues and its role in tumorigenesis and tumor progression, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of N6-methyladenosine (M 6 A) on RNA, represents a putative valuable and specific target for some cancer therapy. In this study, we performed bioinformatic analysis and immunohistochemistry (IHC) to find that IGF2BP3 was highly expressed in tumor epithelial cells and fibroblasts of ovarian cancer (OC), and was associated with poor prognosis, metastasis, and chemosensitivity in OC patients. In particular, we discovered that knockdown IGF2BP3 expression inhibited the malignant phenotype of OC cell lines by decreasing the protein levels of c-MYC, VEGF, CDK2, CDK6, and STAT1. To explore the feasibility of IGF2BP3 as a therapeutic target for OC, a small molecular AE-848 was designed and screened by molecular operating environment (MOE), which not only could duplicate the above results of knockdown assay but also reduced the expression of c-MYC in M2 macrophages and tumor-associated macrophages and promoted the cytokine IFN-γ and TNF-α secretion. The pharmacodynamic models of two kinds of OC bearing animals were suggested that systemic therapy with AE-848 significantly inhibited tumor growth by reducing the expression of tumor-associated antigen (c-MYC/VEGF/Ki67/CDK2) and improving the anti-tumor effect of macrophages. These results suggest that AE-848 can inhibit the growth and progression of OC cells by disrupting the stability of the targeted mRNAs of IGF2BP3 and may be a targeted drug for OC treatment., Competing Interests: None., (AJCR Copyright © 2023.)

Breast cancer is the first most common cancer worldwide, and radiation therapy has a major role to play in locoregional adjuvant treatment. In recent years, we have seen the emergence of adjuvant targeted systemic therapies improving the prognosis of patients at high risk of recurrence. Practices concerning combinations of targeted therapies and locoregional radiation therapy for non-metastatic breast cancers often remain heterogeneous due to the low level of evidence and lack of validated recommendations. This literature review covers immunotherapy, CDK 4/6 inhibitors, PARP inhibitors and anti-Her2 therapies. Combining these targeted systemic therapies with radiation therapy could potentiate local treatment. The optimal therapeutic sequence and fractionation for maximum synergistic effect remain to be defined. However, while efficacy may be enhanced, radiosensitization of healthy tissue may also lead to increased toxicity. It appears possible to continue immunotherapy, trastuzumab, pertuzumab, TDM-1 or lapatinib during locoregional breast and lymph node irradiation. PARP inhibitors and CDK4/6 inhibitors are still to be suspended, due to the lack of data in the adjuvant setting and their short half-life, which does not necessitate prolonged discontinuation. As with the new antibody-drug conjugates, prospective data are needed in conjunction with adjuvant radiation therapy., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

OBJECTIVE: Second-line treatment options for advanced urothelial carcinoma (UC) patients are limited. We aim to investigate the efficacy and toxicities of novel targeted agents (TAs) as salvage treatment for advanced UC by using a meta-analysis. MATERIALS AND METHODS: Relevant trials published from 1994 to 2017 were identified by an electronic search of public databases. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS) and grade 3/4 toxicities were extracted and analyzed using open Meta-Analyst software version 4.16.12 (Tufts University, URL http://tuftscaes.org/open_meta/). RESULTS: Eleven trials with 1,630 previously treated UC patients were included for analysis. The pooled ORR, DCR and 1-year OS for single targeted agent in pre-treated UC patients was 10.7% (95% CI: 10.7-19.6%), 33.2% (95% CI: 25- 41.4%), and 31% (95%: 23.6-39.4%), respectively. Sub-group analysis based on specific targeted agents showed that the efficacy of immune checkpoints inhibitors (ICIs) was significantly higher than that of small molecular tyrosine-kinase inhibitors (TKIs) concerning ORR and 1-year OS. Also, a meta-analysis of three randomized controlled trials showed that the use of TAs in advanced UC patients significantly improved ORR, but not for DCR. As for grade 3 and 4 toxicities, more incidences of severe anemia, fatigue, and diarrhea were observed in the TKIs group than in ICIs group, but not for hypertension. CONCLUSIONS: Our findings support the use of immune checkpoints inhibitors, but not for tyrosine kinase inhibitors as salvage treatment for previously treated UC patients due to its potential survival benefits. [ABSTRACT FROM AUTHOR]

Background: Most patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities. Although comorbidities negatively affect outcomes for patients treated with chemoimmunotherapy, their impact on patients who receive targeted therapies is unknown.Methods: This multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by the Cumulative Illness Rating Scale (CIRS), among patients with CLL treated with ibrutinib.Results: One hundred forty-five patients received ibrutinib (80% in a relapsed/refractory setting). A high burden of comorbidities (CIRS score ≥ 7) was associated with inferior median event-free survival (EFS; 24 vs 37 months; P = .003) and 2-year overall survival (OS; 79% vs 100%; P = .005). In an adjusted Cox model, both EFS and OS worsened with an incremental increase in the CIRS score. Furthermore, comorbidities were associated with an increased risk of ibrutinib dose reduction and therapy discontinuation. CIRS was predictive in both frontline and relapsed CLL, regardless of patient age.Conclusions: Comorbidities portend a poor prognosis among patients with CLL treated with ibrutinib. Prospective studies are needed to optimize the treatment of patients with CLL who have comorbidities. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinum, gemcitabine and doxorubicin compared with CRC. For several of the targeted kinase inhibitors, SI-NET was among the most sensitive solid tumor types. CLL and ovarian cancer were generally the most sensitive tumor types to both cytotoxic drugs and protein kinase inhibitors. SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumor types tested. Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors. Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo. SI-NETs exhibit intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinicopathological factors and currently used biomarkers are not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NET. The great variability in drug sensitivity calls for individualized selection of therapy. [ABSTRACT FROM AUTHOR]

Abstract: Patients with locally advanced rectal cancer (LARC) are at tremendous risk of metastatic diseases. To improve the prognoses of LARC patients, the efficacy of adding targeted agents to neoadjuvant therapy has been investigated by many researchers but remains controversial. A literature search of relevant databases was conducted through December 2016, 804 studies were identified and 32 investigations were ultimately included. A total of 1196 patients from 31 cohorts of 29 studies were eligible for quantitative synthesis in this single‐arm setting meta‐analysis. As pathologic complete response (pCR) shows promise as a prognosis indicator, we focused on pCR rates to evaluate whether adding targeted agents to neoadjuvant therapies improves the outcome of LARC patients. In our study, we revealed pooled estimates of pCR of 27% (95%CI, 21–34%) and 14% (95%CI, 9–21%) for bevacizumab‐relevant cohorts and cetuximab‐relevant cohorts, respectively. The safety of adding targeted agents to neoadjuvant therapy was also evaluated by pooling the data of Grade 3/4 toxicity. In conclusion, our study revealed that adding bevacizumab to the neoadjuvant therapy regimens provides appreciable pCR for LARC patients. Meanwhile, the efficacy of cetuximab remains inconclusive, RCTs with larger scale and better study design that stress more on mutational status are needed. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia-lymphoma (ATL), a rare and aggressive T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1), is associated with a poor prognosis. Evidence-based standard treatment options are lacking and outcomes are generally unsatisfactory, particularly for patients with relapsed or refractory disease. Continued research is contributing to changing treatment landscape as a number of existing and investigational agents are evaluated. We describe the epidemiology of HTLV-1 and ATL, discuss the biology behind the disease, review current treatment practices and guidelines, and provide an overview of emerging therapies in ATL, with a focus on those for relapsed or refractory disease. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic pancreas adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies. In this setting, the molecular and genomic characterization of PDAC have underpinned the use of targeted therapies. To date, the results from targeted agent evaluation have been disappointing with some exceptions. Novel promising strategies depend on biomarker identification and patient selection e.g. germline mutations in DNA repair or mismatch repair genes, where the addition of a platinum agent or checkpoint inhibitor can have a positive impact on survival. This article will review the state-of-the-art treatment of metastatic pancreatic cancer with an emphasis on novel promising therapeutic strategies and an overview on emerging biomarkers. [ABSTRACT FROM AUTHOR]

Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

[Display omitted] • LC screening programs through LDCT showed a reduction of LC-related mortality. • Risk models in LC screening should include patient's characteristics and biomarkers. • LC screening programs will lead to a higher rate of early stage disease diagnoses. • Targeted therapies and immunotherapy will have a key role in perioperative settings. • This new landscape will affect the multidisciplinary team decision making process. Lung cancer (LC) is the leading cause of cancer-related death worldwide, mostly because the lack of a screening program so far. Although smoking cessation has a central role in LC primary prevention, several trials on LC screening through low-dose computed tomography (LDCT) in a high risk population showed a significant reduction of LC related mortality. Most trials showed heterogeneity in terms of selection criteria, comparator arm, detection nodule method, timing and intervals of screening and duration of the follow-up. LC screening programs currently active in Europe as well as around the world will lead to a higher number of early-stage Non Small Cell Lung Cancer (NSCLC) at the diagnosis. Innovative drugs have been recently transposed from the metastatic to the perioperative setting, leading to improvements in terms of resection rates and pathological responses after induction chemoimmunotherapy, and disease free survival with targeted agents and immune checkpoint inhibitors. The present review summarizes available evidence about LC screening, highlighting potential pitfalls and benefits and underlining the impact on the diagnostic therapeutic pathway of NSCLC from a multidisciplinary perspective. Future perspectives in terms of circulating biomarkers under evaluation for patients' risk stratification as well as a focus on recent clinical trials results and ongoing studies in the perioperative setting will be also presented. [ABSTRACT FROM AUTHOR]

Avastin (bevacizumab) is a humanized monoclonal antibody with evident antiangiogenic activity, which blocks vessel endothelial growth factor (VEGF) and prevent its binding with receptors. Chronologically Avastin was among the first (second after trastuzumab) targeted agents approved for clinical practice. Also it is the only targeted agent used in the main malignant solid tumor types: metastatic colorectal cancer, locally recurrent or metastatic breast cancer, metastatic or recurrent nonsquamous non-small cell lung cancer, advanced and/or metastatic renal cell cancer, glioblastoma (stage IV glioma according to WHO classification) and epithelial ovarian, fallopian tube, or primary peritoneal cancer. Therefore Avastin can be defined today as the first and the best, because not one targeted agent has so wide clinical use and indications in practical oncology and moreover practically there were no ineffective clinical trials with Avastin. Also it is necessary to mention that large clinical experience with Avastin demonstrates comparative safety of the agent in different patient’s subgroups and populations.

Opinion Statement: The management of thymic tumours is a paradigm of multidisciplinary collaboration. Chemotherapy may be administered part of curative-intent sequential strategy integrating subsequent surgery or radiotherapy, or as an exclusive treatment if local treatment is not achievable. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. Given the limited activity of cytotoxic agents in the advanced, refractory setting, novel and innovative agents are needed. The better understanding of thymic carcinogenesis may provide a rationale in this setting.Targeted agents approved for other solid tumors that have shown activity in thymic tumors include mTOR, KIT inhibitors, as well as somatostatin analogues. Anti-angiogenic agent sunitinib may be considered a standard in advanced lines of treatment. Ongoing studies are assessing the opportunity of targeting emerging targets, including PI3K, CDK, and immune checkpoint PD-1/PD-L1. [ABSTRACT FROM AUTHOR]

Systematic treatment of adult-type soft tissue sarcoma is evolving. Its role in the neoadjuvant setting is currently experimental, whereas the data on adjuvant chemotherapy are inconclusive. Nevertheless, in clinical practice, neoadjuvant and adjuvant chemotherapy may be considered on an individual basis after multidisciplinary discussion. Systemic therapy has a well-established role in the management of locally advanced and metastatic disease and histology-based treatment approaches are being studied. [ABSTRACT FROM AUTHOR]

The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 (human epidermal growth factor receptor-2 and -3), and BRAF. A major issue with targeted treatment is early identification of patients with primary or secondary drug resistance. Pharmacogenomic research has demonstrated its value in this field, highlighting some tumor mutations that could discriminate responders from non-responders. The tumor genetic profile of the RAS/RAF pathway is needed before treatment with anti-EGFR agents; mutations in EGFR pathway genes have also been explored in relation to antiangiogenic molecules although further data are required prior to their integration into clinical practice. The introduction of immunotherapy has paved the way for a new generation of predictive markers, including genome-wide assessment of the tumor landscape. Furthermore, the development of next generation sequencing technology and non-invasive approaches to analyze circulating tumor DNA will make real-time monitoring of the tumor pharmacogenomic markers possible in the clinical routine, rendering precision medicine available to every patient. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the efficacy and safety of different therapeutic regimens for brain metastases (BMs) from lung cancer (LC). A total of 13 controlled trials (1,783 cases) involving chemotherapy, tyrosine kinase inhibitors or endostatin plus radiotherapy (combination group) vs. radiotherapy alone group were identified from PubMed. Compared with the radiotherapy alone group, the combination group resulted in a significant benefit for objective response rate (ORR) [risk ratio (RR), 1.38; 95% confidence interval (CI), 1.19‑1.60; P<0.0001], notably prolonged the time to central nervous system progression [CNS‑TTP; hazard ratio (HR), 0.71; 95% CI, 0.57‑0.90; P=0.004] and progression‑free survival (PFS; HR, 0.60; 95% CI, 0.44‑0.83; P=0.002); however, failed in prolonging the overall survival (OS; HR, 0.80; 95% CI, 0.61‑1.05; P=0.11) with a higher overall severe adverse events (AEs, Grade ≥3; RR, 2.57; 95% CI, 1.24‑5.35; P=0.01). Notably, subgroup analysis demonstrated that targeted therapy plus radiotherapy possessed a superior OS compared with radiotherapy alone (HR, 0.58; 95% CI, 0.37‑0.90; P=0.01) with mild non‑hematological toxicity and without severe hematotoxicity. The present study demonstrated that targeted agents plus radiotherapy possessed desirable effects with mild adverse events. Secondary to best, chemoradiotherapy is an alternative option for patients without suitable molecular targets. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is>70 years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living and social support. Comorbidity scoring and geriatric assessment tools are helpful in achieving such multidimensional evaluation in a systematic manner. The introduction of new drugs including novel monoclonal antibodies and kinase inhibitors offers enhanced opportunities for the treatment of elderly patients with CLL. This position paper of a Task Force of the International Society of Geriatric Oncology (SIOG) reviews currently available evidence relevant to such patients. All types of elderly patient (i.e. chronological age>65-70 years) are considered, from robust (fit) to vulnerable (unfit) to the terminally ill. Among the topics covered are the following: (i) the relationship between chronological age, prognosis and survival, (ii) assessment of biological aging, (iii) biological age as a determinant of treatment feasibility and tolerance and (iv) tailoring of both first and further-line treatment to the circumstances of the individual patient. [ABSTRACT FROM AUTHOR]

Introduction: To examine the magnitude of the clinical benefit from first-line tyrosine kinase inhibitors (TKIs) advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR)-mutations. Areas covered: The present evaluation was restricted to pivotal phase III RCTs in first-line for advanced NSCLC with activating EGFR-mutations. We have subsequently applied the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) to the above pivotal phase III RCTs, to derive a relative ranking of the magnitude of clinically meaningful benefit. Our study evaluated 8 phase III RCTs (including 1710 patients). The ESMO-MCBS reached high grade (grade 4) for all TKIs treatments with at least one phase III RCT for each TKI. Expert commentary: Combining pharmacological costs of drugs with the measure of efficacy, afatinib has the lowest difference in costs per month-PFS gained and a comparable high grade of magnitude of clinical benefit. [ABSTRACT FROM AUTHOR]

Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare malignancies arising from the thymus gland. The optimal management requires a multidisciplinary approach. Standard first-line systemic treatment involves cytotoxic chemotherapeutic regimens; however, alternative options for systemic treatment are required. Current research focuses on the unique profile of immune-related pathogenic mechanisms of TETs, involving an overlap with certain autoimmune phenotypes, as well as on determining the landscape of oncogenic molecular alterations and the role of tumor angiogenesis. The aim of the present review is to summarize the current clinical investigation on immunotherapy and targeted agents in the management of TETs. Regarding immune checkpoint inhibitors, efficacy results are promising in certain subsets of patients; however, caution is required concerning their toxicity. Anti-angiogenic agents, mainly potent small-molecule inhibitors, have demonstrated antitumor activity in TETs, whereas other targeted agents, including KIT inhibitors and epigenetic agents, are associated with encouraging, yet still modest results for unselected populations, in the absence of predictive biomarkers. Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. [ABSTRACT FROM AUTHOR]

Introduction: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings., Materials and Methods: Using deidentified electronic medical records from the CLL Collaborative Study of Real-World Evidence, premature treatment discontinuation was assessed among FCR, BR, BTKi-based, and BCL-2-based regimen cohorts., Results: Of 1364 1L patients (initiated in 1997-2021), 190/13.9% received FCR (23.7% discontinued prematurely); 255/18.7% received BR (34.5% discontinued prematurely); 473/34.7% received BTKi-based regimens, of whom 28.1% discontinued prematurely; and 43/3.2% received venetoclax-based regimens, of whom 16.3% discontinued prematurely (venetoclax monotherapy: 7/0.5%, of whom 42.9% discontinued; VG/VR: 36/2.6%, of whom 11.1% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 25/13.2%; BR: 36/14.1%; BTKi-based regimens: 75/15.9%) and disease progression (venetoclax-based: 3/7.0%). Of 626 2L patients, 20/3.2% received FCR (50.0% discontinued); 62/9.9% received BR (35.5% discontinued); 303/48.4% received BTKi-based regimens, of whom 38.0% discontinued; and 73/11.7% received venetoclax-based regimens, of whom 30.1% discontinued (venetoclax monotherapy: 27/4.3%, of whom 29.6% discontinued; VG/VR: 43/6.9%, of whom 27.9% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 6/30.0%; BR: 11/17.7%; BTKi-based regimens: 60/19.8%; venetoclax-based: 6/8.2%)., Conclusion: The findings of this study highlight the continued need for tolerable therapies in CLL, with finite therapy offering a better tolerated option for patients who are newly diagnosed or relapsed/refractory to prior treatments., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Brain metastasis (BM) from colorectal cancer (CRC) is rare and associated with poor prognosis. The mainstay of treatment for BM from CRC is radiotherapy, systemic treatment options for CRC can include novel targeted agents, conventional chemotherapy or a combination of both. Nevertheless, the efficacy of these systemic treatment options against BM from CRC is not yet fully established. Cetuximab, a monoclonal antibody, has been shown to be effective in patients with KRAS wild-type metastatic CRC. The combination of cetuximab with oxaliplatin-based chemotherapy is commonly utilized as a systemic treatment for metastatic CRC. Hereby, we report a case of BM from CRC with significant response after capecitabine and oxaliplatin (XELOX) combined with cetuximab.

Lung cancer continues to be the most common cause of cancer-related mortality worldwide. Recent advances in molecular diagnostics and immunotherapeutics have propelled the rapid development of novel treatment agents across all cancer subtypes, including lung cancer. Additionally, more pharmaceutical therapies for lung cancer have been approved by the US Food and Drug Administration in the last 5 years than in previous two decades. These drugs have ushered in a new era of lung cancer managements that have promising efficacy and safety and also provide treatment opportunities to patients who otherwise would have no conventional chemotherapy available. In this review, we summarize recent advances in lung cancer therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to drugs in their class or are a completely new class of drugs with novel mechanisms of action. We have divided our discussion into targeted agents, immunotherapies, and antibody drug conjugates for small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). We briefly review the emerging agents and ongoing clinical studies. We have attempted to provide the most current review on emerging therapeutic agents on horizon for lung cancer. [ABSTRACT FROM AUTHOR]

Background Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed. Methods We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies. Our effort was to highlight the available treatment options in the setting of recurrent/metastatic disease. Results Although there have been important advances in the management of women with cervical cancer, the optimal treatment for patients with locally recurrent and metastatic disease after platinum failure is still problematic. Overall, there is a trend in terms of longer overall survival (OS) and better quality of life for the combination of cisplatin/paclitaxel (PC) as compared to the doublets of cisplatin/topotecan (TC), cisplatin/vinorelbine (VC), and cisplatin/gemcitabine (GC). Currently available single agents beyond first-line platinum-based therapy have limited efficacy in this setting and include topoisomerase inhibitors, vinca alkaloids, taxanes, alkylating agents and antimetabolites. Several targeted therapies have demonstrated activity in advanced cervical cancer. Bevacizumab has been evaluated in a phase III trial using doublets of cisplatin with paclitaxel or topotecan and has been approved in the first-line setting by the U. S. Food and Drug Administration. Selective targeting of angiogenic kinases by tyrosine kinase inhibitors (TKIs) may represent a novel therapeutic tool in this setting, but its use alone or in combination with CT is still investigational. Early reports have implicated PI3KCA somatic mutations suggesting that mTOR-targeted agents should be explored in this disease. Development of the immune checkpoint programmed cell death 1 (PD-1) and T-lymphocyte–associated molecule-4 (CTLA-4) inhibitors have been of considerable interest, leading to ongoing phase II studies in patients with advanced cervical cancer. Conclusions Progress in the management of recurrent and advanced cervical cancer patients has been slow and restricted to palliative intent. These patients should be considered for clinical trials of novel targeted agents and/or immunotherapy. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common extra-cranial solid tumor encountered in childhood and accounts for 15% of pediatric cancer-related deaths. Although there has been significant improvement in the outcomes for patients with high-risk disease, the therapy needed to achieve a cure is quite toxic and for those that do experience a disease recurrence, the prognosis is very dismal. Given this, there is a tremendous need for novel therapies for children with high-risk neuroblastoma and the molecular discoveries over recent years provide hope for developing new, less toxic, and potentially more efficacious treatments. Here I discuss many of the molecular aberrations identified thus far in neuroblastoma, as well as the agents in development to target these changes. The progress made in both the preclinical arena and in early phase drug development provide much promise for the future of precision medicine in neuroblastoma.

Antibody-drug conjugates (ADCs) have become a credentialled class of anticancer drugs for both solid and hematological malignancies, with regulatory approvals mainly as single agents. Despite extensive preclinical and clinical efforts to develop rational ADC-based combinations, to date only a limited number have demonstrated survival improvements over standard of care. The most appealing partners for ADCs are those that offer additive or synergistic effects on tumor cells or their microenvironment without unacceptable overlapping toxicities. Coadministration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents and immune checkpoint inhibitors (ICIs) represent active forerunners. Through the identification of targets with tumor-specific expression, improved conjugation technologies, and novel linkers and payloads offering superior therapeutic indices, the next generation of ADCs brings optimism to combinatorial approaches., Competing Interests: Declaration of interests L.L.S. has consulting/advisory arrangements with Merck, Pfizer, AstraZeneca, Roche, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, Daiichi Sanyko, Coherus, Marengo, and InteRNA; stock ownership of Agios (spouse); leadership position in Treadwell Therapeutics (spouse); and their institution receives clinical trials support from Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Intensity Therapeutics, Mirati Therapeutics, and Shattucks. The rest of the authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)