This study aimed to explore advances in biomarkers related to anti-angiogenic therapy in patients with non-small cell lung cancer (NSCLC), thereby enhancing treatment selection, advancing personalized and precision medicine to improve treatment outcomes and patient survival rates. This article reviews key discoveries in predictive biomarkers for anti-angiogenic therapy in NSCLC in recent years, such as (1) liquid biopsy predictive biomarkers: studies have identified activated circulating endothelial cells (aCECs) via liquid biopsy as potential predictive biomarkers for the efficacy of anti-angiogenic therapy; (2) imaging biomarkers: advanced imaging technologies, such as dynamic contrast-enhanced integrated magnetic resonance positron emission tomography (MR-PET), are used to assess tumor angiogenesis in patients with NSCLC and evaluate the clinical efficacy of anti-angiogenic drugs; (3) genetic predictive biomarkers: research has explored polymorphisms of Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) and vascular endothelial growth factor-A (VEGF-A), as well as how plasma levels of VEGF-A can predict the outcomes and prognosis of patients with non-squamous NSCLC undergoing chemotherapy combined with bevacizumab. Despite progress in identifying biomarkers related to anti-angiogenic therapy, several challenges remain, including limitations in clinical trials, heterogeneity in NSCLC, and technical hurdles. Future research will require extensive clinical validation and in-depth mechanistic studies to fully exploit the potential of these biomarkers for personalized treatment.

Background: Limited-stage small cell lung cancer (LS-SCLC) is a highly aggressive tumor characterized by a poor prognosis. While concurrent chemoradiotherapy (CCRT) remains the standard treatment, the high rates of recurrence and poor long-term survival highlight the pressing need for novel therapeutic approaches. Purpose: In recent years, the introduction of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has opened new avenues for the treatment of LS-SCLC. This review highlights the clinical advancements of ICIs in CCRT, consolidation therapy, and neoadjuvant therapy, emphasizing their potential to improve progression-free survival (PFS) and overall survival (OS). This review also discusses management of immunotherapy-related side effects. Research Design: This is a review article that synthesizes recent research findings on immunotherapy for LS-SCLC. Study Sample: Not applicable (review of existing literature). Data Collection and/or Analysis: This review summarizes key studies exploring the application of immunotherapy in limited-stage small cell lung cancer.Additionally, it examines the role of the tumor microenvironment, tumor mutation burden (TMB), and Programmed cell death 1 ligand 1(PD-L1) as biomarkers for predicting the efficacy of immunotherapy. Results: This review emphasizes their potential to improve PFS and OS. Conclusions: Despite the significant advancements in research, the use of ICIs in LS-SCLC continues to face challenges, including the identification of optimal treatment regimens, validation of long-term efficacy, and development of personalized predictive biomarkers. Future research should prioritize large-scale, multicenter clinical trials to refine combination therapy strategies, establish customized treatment approaches, and enhance patient outcomes.

Objective: This study evaluated the hepatotoxicity risk of anaplastic lymphoma kinase ( ALK)/ROS1- tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: A retrospective analysis of 19,611 FAERS reports related to ALK/ROS1 -TKIs (2011–2025) identified 1495 hepatotoxicity cases. Disproportionality analysis (reporting odds ratio, proportional reporting ratio, empirical Bayes geometric mean) assessed six ALK- TKIs and three ROS1- TKIs. Temporal trends, clinical outcomes, and differences across TKI generations were examined. Results: Second-generation ALK -TKIs (e.g. alectinib) showed the most favorable hepatic safety profile, with the lowest observed mortality (3.5%) and hospitalization (13.0%). First-generation TKIs (crizotinib, ceritinib) and newer agents (lorlatinib, entrectinib) were associated with higher fatality rates (12.0%–13.2%). Most hepatotoxic events (51.9%) occurred within one month; however, 8.37% developed after one year. Mechanistically, the lower risk with second-generation TKIs may reflect less CYP-dependent metabolism and greater target selectivity. Conclusion: Analysis of FAERS reports indicates substantial heterogeneity in hepatotoxicity risk among ALK inhibitors. Second-generation agents showed lower mortality and hospitalization than first- and third-generation counterparts. Crizotinib, ceritinib, and lorlatinib were associated with notably high fatality rates, warranting continuous hepatic monitoring. ROS1 inhibitors (e.g. entrectinib) may exhibit distinct hepatotoxicity profiles. These findings should be interpreted cautiously given inherent reporting biases. Future priorities include prospective studies, biomarker-integrated risk stratification, mechanistic investigation, and AI-enhanced monitoring to optimize the risk–benefit profile of ALK/ROS1 -TKIs.

Original Article Efficacy and safety of antibody-drug conjugates in the treatment of non-small cell lung cancer: a systematic review and meta-analysis of prospective clinical trials Xiaoni Jin, Weixing Zhao, Bo Li, Yujia Gu, Zirui Li, Wanjing Guo, Xinxin Lu, Jun Jiang

Background: This study systematically assesses the efficacy of immunotherapy as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) and bone metastases who lack driver gene mutations. This analysis draws on data from randomized controlled trials to support individualized treatment strategies. Methods: Randomized controlled trials published up to October 1, 2024, were retrieved from PubMed, EMBASE, the Cochrane Library, and the Web of Science. Statistical analyses were conducted using RevMan 5.4 and STATA 17.0, with the results presented in forest plots. Progression-free survival (PFS) and overall survival (OS) were analyzed using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024604768). Results: Meta-analysis demonstrated a significant improvement in OS and PFS for patients with bone metastases receiving immunotherapy (OS: HR: 0.81, 95% CI: 0.71-0.92; PFS: HR: 0.78, 95% CI: 0.62-0.98). Although the survival benefit of immunotherapy was lower in patients with bone metastases than in those without, it was superior to chemotherapy. Conclusions: Among patients with driver gene-negative NSCLC and bone metastases, immunotherapy significantly improved OS and PFS, thus supporting its role as an effective first-line treatment. Further large-scale trials are recommended to enhance treatment precision and validate these findings.