Additionally, Wermke et al. reported promising results from a Phase I trial of obrixtamig, a DLL3/CD3 T-cell engager, in patients with DLL3-positive small cell lung cancer (SCLC). This study focused on dose escalation and safety, indicating potential for this novel therapeutic approach in targeting SCLC (ref: Wermke doi.org/10.1200/JCO-25-00363/). In the context of SCLC, Cui et al. identified IFITM3 as a critical regulator of immunosensitivity, linking its expression to the efficacy of anti-PD-1/-L1 therapies (ref: Cui doi.org/10.1186/s12943-025-02383-x/). Redin et al. demonstrated that dasatinib can remodel the tumor microenvironment, enhancing the infiltration of immune cells and sensitizing SCLC to immunotherapy, thus providing a rationale for combination strategies (ref: Redin doi.org/10.1158/0008-5472.CAN-24-2772/). Together, these findings underscore the importance of understanding immune evasion mechanisms and the potential of innovative combination therapies to improve outcomes for lung cancer patients.

In addition, Sun et al. conducted a single-cell transcriptomic analysis of post-tuberculosis lung tissues, uncovering molecular signatures associated with senescence and inflammation, which may contribute to lung cancer pathogenesis (ref: Sun doi.org/10.1038/s41564-025-02050-3/). Ma et al. explored the transition from cellular senescence to pyroptosis in SCLC, revealing mechanisms that contribute to cancer recurrence post-chemotherapy, thus highlighting the need for strategies to address these cellular fate transitions (ref: Ma doi.org/10.1126/sciadv.adw1553/). Mozzarelli et al. identified RIT1 mutations as actionable targets in lung adenocarcinoma, demonstrating that these mutations lead to oncogenic transformation and dysregulation of signaling pathways (ref: Mozzarelli doi.org/10.1158/0008-5472.CAN-24-3819/). Together, these findings underscore the importance of understanding the genomic landscape of lung cancer to inform therapeutic strategies and improve patient outcomes.

Durm et al. conducted a randomized Phase II study comparing consolidation immunotherapy with nivolumab and ipilimumab versus nivolumab alone following chemoradiotherapy for unresectable stage IIIA/IIIB NSCLC. Their findings indicated that nivolumab alone significantly improved progression-free survival compared to historical controls, emphasizing the potential of immunotherapy in this patient population (ref: Durm doi.org/10.1136/jitc-2024-010316/). Chen et al. performed a systematic review and meta-analysis on cancer vaccines in advanced NSCLC, demonstrating their clinical efficacy and safety, particularly in squamous cell carcinoma, thus providing valuable insights for future therapeutic applications (ref: Chen doi.org/10.1016/j.eclinm.2025.103369/). These findings collectively underscore the importance of clinical trials in identifying effective treatment strategies and the need for ongoing research to optimize lung cancer management.

Wu et al. presented a novel cyclized bivalent aptamer-based protein degrader targeting receptor tyrosine kinases, demonstrating its efficacy in overcoming resistance to EGFR-TKIs in NSCLC. This innovative approach highlights the potential for targeted therapies to address drug resistance and improve patient outcomes (ref: Wu doi.org/10.1021/acsnano.5c03120/). The findings from these studies underscore the importance of understanding the tumor microenvironment and metastatic mechanisms to inform the development of effective therapeutic strategies for lung cancer.

Kim et al. investigated the role of NOTCH1 in reversing immune suppression in SCLC, demonstrating that high NOTCH1 expression is associated with improved survival when combined with immune checkpoint blockade (ref: Kim doi.org/10.1172/JCI185423/). Yu et al. performed a longitudinal pharmacogenomic analysis to identify therapeutic candidates for EGFR-TKI resistance subclones, revealing the dynamic nature of tumor evolution and the challenges it poses for effective treatment (ref: Yu doi.org/10.1038/s12276-025-01493-2/). These studies highlight the importance of understanding resistance mechanisms and the potential for targeted therapies to overcome these challenges in lung cancer treatment.

Shimauchi et al. explored the enhanced internalization of HER2 in NSCLC with mutations, demonstrating that clathrin-dependent endocytosis mediates this process and contributes to the efficacy of HER2-targeted antibody-drug conjugates (ref: Shimauchi doi.org/10.1038/s41416-025-03126-x/). Amidi et al. developed a two-step vision transformer approach to predict ROS1 and ALK fusions in NSCLC from H&E slides, showcasing the potential of artificial intelligence in improving diagnostic precision (ref: Amidi doi.org/10.1038/s41698-025-01037-x/). These findings highlight the ongoing advancements in biomarker discovery and diagnostic methodologies, which are essential for optimizing lung cancer management.

Zhang et al. investigated the role of phosphodiesterase 1A in NSCLC progression, revealing its interaction with YTHDF2 and implications for targeted therapy (ref: Zhang doi.org/10.7554/eLife.98903/). The findings from these studies underscore the need for innovative combination strategies that leverage the unique vulnerabilities of lung cancer to improve patient outcomes and address the challenges of treatment resistance.

Amrane et al. analyzed the efficacy of first-line treatments for advanced pulmonary sarcomatoid carcinomas, revealing that combination therapies yielded improved progression-free survival compared to chemotherapy alone (ref: Amrane doi.org/10.1016/j.esmoop.2025.105343/). Shimauchi et al. investigated the internalization of HER2 in NSCLC with mutations, highlighting the potential of HER2-targeted therapies in improving patient outcomes (ref: Shimauchi doi.org/10.1038/s41416-025-03126-x/). These findings emphasize the importance of addressing health disparities and optimizing treatment strategies to enhance outcomes for all lung cancer patients.