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Background: Several head-to-head meta-analyses have compared the efficacy and safety of different first-line treatments in patients with EGFR mutation-positive (M+) advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC). However, there is a lack of comprehensive evaluation encompassing multiple treatment strategies. Our objective is to conduct a network meta-analysis that includes various treatment modalities, enabling both direct and indirect comparisons for a more thorough assessment. Methods: We conducted a search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception until May 8, 2024, to identify eligible randomized controlled trials (RCTs). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary outcomes included objective response rate (ORR) and grade 3 or higher adverse events (≥3AEs). Stata 15.0 and R 4.3.2 software were utilized for the network meta-analysis. Results: A total of 30 RCTs, comprising 8654 participants, were included. The study encompassed the following 19 treatments: Chemotherapy; Afatinib; Afatinib + Cetuximab; Apatinib + Gefitinib; Befotertinib; Cetuximab + Chemotherapy; Erlotinib; Erlotinib + Bevacizumab; Erlotinib + Chemotherapy; Gefitinib; Gefitinib + Chemotherapy; Gefitinib + Olaparib; Icotinib; Icotinib + Chemotherapy; Lazertinib; Naquotinib; Osimertinib; Osimertinib + Bevacizumab; Osimertinib + Chemotherapy. The network meta-analysis results indicated that, in terms of PFS, Osimertinib + Chemotherapy (SUCRAs: 93.4%) and Osimertinib (SUCRAs: 84.61%) were the most effective. Regarding OS, Lazertinib (SUCRAs: 89.72%), Gefitinib (SUCRAs: 72.07%), and Osimertinib + Chemotherapy (SUCRAs: 70.74%) emerged as the top three options. Afatinib (SUCRAs: 92.27%) was associated with the best ORR improvement. For ≥3AEs, Afatinib (SUCRAs: 74.93%) and Osimertinib (SUCRAs: 69.42%) were likely the best choices. Conclusion: Current evidence suggests that, considering both survival and safety, Osimertinib stands out as the preferred first-line treatment for untreated EGFR M + advanced or metastatic nsq-NSCLC. Notably, the combination of Osimertinib with chemotherapy demonstrated superior survival benefits. However, due to the limitations in the number and quality of included studies, these conclusions await further validation through more high-quality research. Systematic review registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42024562981 , identifier CRD42024562981. [ABSTRACT FROM AUTHOR]

In 2020, we reported on a case involving a 68-year-old male patient with a rare instance of pulmonary pleomorphic carcinoma exhibiting high PD-L1 expression. The patient experienced significant therapeutic success with the use of camrelizumab, achieving partial tumor remission. Following the publication of that report, the patient continued on camrelizumab at a dose of 200 mg/dl for 27 cycles, subsequently transitioning to a combination of camrelizumab and bevacizumab for eight cycles. Due to elevated blood pressure, the regimen was adjusted back to monotherapy with camrelizumab. As of July 9, 2024, the patient remains alive with a satisfactory quality of life. This follow-up report, coupled with a review of the literature from 2021 to 2024 on pulmonary pleomorphic carcinoma and its immunotherapeutic approaches, aims to present new insights and innovative strategies for treating this rare form of cancer. [ABSTRACT FROM AUTHOR]

Aim: Gastric cancer is the third leading cause of cancer-related mortality and the fifth most common cancer globally. In China, many patients are diagnosed at an advanced stage and cannot be operated on, so the prognosis is very poor. The role of maintenance therapy after first-line chemotherapy in gastric cancer is still unclear. Apatinib is a small-molecule VEGFR-2 TKI and is currently approved for third-line treatment after failure of second-line chemotherapy for advanced gastric cancer. In this article, we use case reports to illustrate its effectiveness and to study what effective maintenance treatments are available for gastric cancer. Methods: The main treatment is chemotherapy and targeted therapy. We reported a 68-year-old man with a diagnosis of advanced gastric cancer with liver metastasis. From 12/2014 to 05/2015 Oxaliplatin + S-1(dose) chemotherapy for 6 cycles, the efficacy of partial response (PR) evaluation. After the patient's oral S-1 + Apatinib (dose) to maintain the therapeutic usage and dosage, the patient is well tolerated, the tumor is reviewed regularly, and the condition is stable. The patient was finally infected with the COVID-2019 in May 2023, resulting in death after ineffective treatment. Results: After Oxaliplatin combined with S-1 regimen, the effect was up to PR. S-1 combined with Apatinib maintenance therapy after first-line chemotherapy, the patient has survived for more than 7 years without progression. Conclusions: The current treatment of advanced gastric cancer is not satisfactory. The combined application of S-1 and Apatinib in gastric cancer maintenance therapy deserves further study. Maintenance therapy for gastric cancer has attracted wide attention, and more large-scale clinical research is under way. [ABSTRACT FROM AUTHOR]

Background: The low incidence and poor prognosis primary trastuzumab resistance (PTR) in HER2-positive breast cancer has limited research into possible treatments. Thus, it remains unclear whether this group of patients could benefit from nontargeting HER2 antiangiogenic therapy. Patients and Methods: We collected the medical data for HER2-positive patients with PTR who received apatinib 250 mg and trastuzumab-based chemotherapy (ATBC) between March 18, 2017, and March 31, 2022. All patients had progressed on ≥2 anti-HER2 treatments, including trastuzumab and small molecular tyrosine kinase inhibitors. We evaluated tumor response and safety profiles to ATBC over a median follow-up time of 34.5 months. Results: A total of 198 consecutively HER2-positive metastatic breast cancer patients were reviewed; 20 were PTR and received ATBC. The clinical benefit rate of the total cohort was 55.0%. No patient showed a complete response. The median PFS and overall survival (OS) of the entire cohort was 5.7 months (95% CI 2.9–8.5) and 24.6 months (95% CI 6.9–42.4), respectively. The estimated 2-year survival rate was 46.7% (95% CI 38.4–81.6%). The most common nonhematologic adverse events were hypertension (70.0%), hand-foot skin reaction (55.0%), proteinuria (40.0%), and cardiovascular decrease of LVEF (20.0%). No new toxicities were observed. Conclusion: ATBC had favorable effects for PTR breast cancer patients in later line treatment. The toxicity of the triple-combination regimen was tolerable; thus, further research should focus on identifying PTR patients who could benefit from ATBC. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of drug eluting bead transarterial chemoembolization (D-TACE) combined with apatinib/camrelizumab in patients with advanced hepatocellular carcinoma (HCC) and hepatic arterioportal shunts (APSs). Methods From January 2021 to December 2022, the consecutive medical records of patients with advanced HCC and APS receiving D-TACE combined with apatinib/camrelizumab were reviewed for eligibility. Overall survival (OS), progression-free survival (PFS), tumour response, and adverse events (AEs) were assessed. Results A total of 23 patients were included in this study, with a median follow-up of 11 months (range, 2-26 months). Eight patients (34.8%) achieved partial response; 13 (56.5%), stable disease; and 2 (8.7%), progressive disease. The objective response and disease control rates were 34.8% and 91.3%, respectively. The OS and PFS rates were 11 and 7 months, respectively. Multivariate analysis indicated that the tumour number was an independent prognostic factor for PFS. AEs occurred in 19 patients after oral apatinib treatment and in 8 patients after camrelizumab treatment. No treatment-related death occurred during the study period. Conclusions D-TACE combined with apatinib/camrelizumab showed meaningful efficacy and controllable AEs in these patients, making it a promising treatment option. Advances in knowledge (1) We investigated a new treatment strategy for patients with advanced HCC and hepatic APS and (2) D-TACE combined with apatinib/camrelizumab demonstrated meaningful efficacy and manageable AEs, making it a promising treatment option. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aimed to develop a population pharmacokinetic (PPK) model for oral apatinib in Chinese oncology patients and investigate the factors influencing the pharmacokinetics of apatinib. Methods We gathered 199 blood concentration monitoring data points from 91 inpatient oncology participants receiving oral apatinib at the Third Affiliated Hospital of Soochow University. Covariates, such as age, gender, body weight, and indices of liver and renal function, were examined to assess their influence on the pharmacokinetic parameters of apatinib. The PPK model was developed using the nonlinear mixed-effects modeling procedure (NONMEM), and model validation was conducted using the bootstrap method and normalized prediction distribution error (NPDE) method. Results The structural model adopted a one-compartment structure with first-order elimination. Notably, aspartate aminotransferase (AST) and the co-administered drug type emerged as primary covariates affecting apatinib clearance (CL/F). The finalized model was expressed as CL/F (L/h) = 56.7 × (AST/26.6)−0.298 × θ, when apatinib was combined with monoclonal antibodies, θ was 1; when combined with paclitaxel, θ was 0.58; when combined with other drugs (e.g., platinum, capecitabine, or the combination of tegafur, gimeracil, and oteracil potassium), θ was 1.60; When used as monotherapy, θ was 1.38. V/F = 674 L, and the absorption rate constant (Ka) was fixed at 0.08 h−1. Bootstrap results affirmed the model’s reliability and stability, while NPDE outcomes attested to the model’s fit. Conclusion Our study successfully established a PPK model for apatinib in oncology patients, revealing that liver function status and co-administered drug types significantly impacted apatinib CL/F. This finding underscored the potential necessity for dose adjustments to optimize efficacy, particularly in patients undergoing different chemotherapy regimens involving apatinib.

Abstract Stage I non-small cell lung cancer (NSCLC) accounts for about 15% of incident cancer cases. Prognosis is poor, with a metastasis and recurrence rate of 38% within 2 years of surgery and an overall 5-year survival rate of 54–60%. Here, we report successful apatinib monotherapy of early NSCLC in a patient who had declined surgery, radiofrequency ablation, and immunotherapy. The patient received apatinib for 64 months without clinical, laboratory, or radiographic evidence of disease progression. The curative effect was judged to be stable and safe.The role of apatinib as monotherapy for patients with early stage NSCLC who are not candidates for surgery or radiotherapy, or as an adjunct to standard therapy, deserves further study.

Abstract Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis.

Abstract Background Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

Fengyi Yang,1,2,* Qiaoyan Dong,3,* Zhuo Chen,1,2,* Benjian Gao,1,2,* Dongning Zheng,1,2 Rui Wang,1,2 Shu Qin,1,2 Fangyi Peng,1,2 Ming Luo,1,2 Jin Yang,1,2 Mengmei Nie,4 Bo Li,1,2 Xiaoli Yang1,2 1Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Luzhou Senior High School, Luzhou, 646000, People’s Republic of China; 4Department of Urological Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Li; Xiaoli Yang, Email liboer2002@126.com; 344920646@qq.comPurpose: The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver cancer therapy.Patients and Methods: A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model.Results: The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to other groups.Conclusion: We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC.Keywords: metal-organic frameworks nanoparticles, apatinib, drug-targeting delivery, ferroptosis therapy, hepatocellular carcinoma

Ovarian cancer is one of the most common gynecological malignancies. The current first-line treatment strategies for advanced ovarian cancer include surgery, chemotherapy, and maintenance therapy. Bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) are primary maintenance treatments for advanced ovarian cancer. Previously, many patients declined these therapies before medicare coverage because of high costs. Bevacizumab and apatinib are anti-tumor angiogenic agents. In this case study, we describe a patient with advanced ovarian cancer who underwent neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. She declined bevacizumab and PARPi maintenance therapy owing to the prohibitive expenses. The patient was administered off-label apatinib and achieved a progression-free survival of 54 months. Thus, apatinib may offer substantial therapeutic value as a first-line maintenance therapy in advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective(s): This study investigated the inhibitory effect of apatinib on lung cancer cells with high expression of vascular endothelial growth factor-2 (VEGFR-2) and on inducing cellular autophagy and drug resistance. Materials and Methods: The expression of VEGFR-2 was detected using western blotting and RT-PCR. Cell proliferation was measured using the CCK8 and colony formation assays. The cell apoptosis rate was determined using flow cytometry and tunnel assay. Cellular autophagy was detected by measuring the expression of LC3-II using Western blotting and cellular immunofluorescence. The inhibitory effect of apatinib on lung cancer cells and transplanted tumors was observed after treatment with the autophagy inhibitor chloroquine. Results: Apatinib dose-dependently inhibited the proliferation of H1975 and H446 cells; it induced apoptosis via the PARP and caspase-3 pathways in H1975 and H446 cells and effectively inhibited the growth of transplanted tumors. Apatinib induced autophagy in a dose-dependent manner in H1975 and H446 cells. The inhibitory effect of apatinib on cells and the promotion of apoptosis were significantly enhanced after treatment with chloroquine. Immunohistochemistry showed that combining apatinib with chloroquine could reduce the expression of CD31 and Ki67 and increase the expression of caspase-3. Conclusion: Apatinib inhibits proliferation and induces apoptosis in H1975 and H1446 lung cancer cells with high VEGFR2 expression and autophagy in H1975 and H446 cells. [ABSTRACT FROM AUTHOR]

Nonsmall cell lung cancer (NSCLC), one of the most aggressive malignancies globally, is characterized by poor prognosis and limited life expectancy. Epigallocatechin‐3‐gallate (EGCG), a natural polyphenol found in green tea, has emerged as a promising anticancer agent due to its potent antitumor properties. However, the role and the underlying mechanisms of EGCG in NSCLC remain poorly understood. Hence, this research aimed to explore the effect of EGCG on the antitumor effect of apatinib in NSCLC through vascular endothelial growth factor (VEGF)‐regulated glycolysis. Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2'‐deoxyuridine staining, wound healing, transwell, terminal deoxynucleotidyl transferase dUTP nick‐end labeling, and flow cytometry assays were carried out to evaluate the proliferation, migration, invasion, and apoptosis of H1299 cells, respectively. Furthermore, western blot analysis was used to detect the expressions of VEGF, p‐vascular endothelial growth factor receptor‐2, hypoxia‐inducible factor 1α, neuropilin‐1, phosphorylated‐phosphatidylinositol 3‐kinase, and phosphorylated‐AKT. The transfection efficiency of H1299 cells with VEGF overexpression plasmid was also assessed by western blot analysis. Glycolysis was analyzed by estimating extracellular acidification rate, lactate concentration, glucose uptake, and the expressions of lactate dehydrogenase A, pyruvate kinase M2, and hexokinase 2. The results demonstrated that VEGF activated glycolysis in NSCLC cells. EGCG alone and apatinib alone or in combination inhibited cell viability, proliferation, invasion, migration, and glycolysis whereas promoted apoptosis in NSCLC cells. EGCG regulated glycolysis levels in NSCLC through VEGF overexpression, and enhanced the antitumor effect of apatinib in NSCLC through VEGF‐regulated glycolysis. Taken together, EGCG strengthened the protective effects of apatinib in NSCLC through glycolysis mediated by VEGF. [ABSTRACT FROM AUTHOR]