Recent studies have highlighted the critical role of immunotherapy in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Xie et al. conducted a phase II trial evaluating sintilimab, an anti-PD-1 antibody, combined with chemotherapy, revealing that durable responses are limited to a small subset of patients. This study emphasized the need for comprehensive immune profiling to identify potential biomarkers for predicting treatment response (ref: Xie doi.org/10.1038/s41392-025-02252-5/). Similarly, Cheng et al. reported on the ASTRUM-005 trial, which demonstrated that serplulimab plus chemotherapy significantly improved overall survival compared to chemotherapy alone, identifying a 15-protein signature associated with better outcomes (ref: Cheng doi.org/10.1002/cac2.70032/). These findings underscore the importance of local tumor microenvironment and immune-genomic signatures in tailoring immunotherapy strategies for ES-SCLC patients. In the context of non-small cell lung cancer (NSCLC), Ricciuti et al. explored the efficacy of neoadjuvant PD-1 and PD-L1 blockade combined with chemotherapy for patients with borderline resectable and unresectable stage III NSCLC, showing promising pathological and survival outcomes (ref: Ricciuti doi.org/10.1001/jamaoncol.2025.1115/). Furthermore, Heyward's analysis of immune checkpoint inhibitors (ICIs) revealed significant variability in the harm-benefit ratio across different patient subgroups, emphasizing the need for personalized treatment approaches (ref: Heyward doi.org/10.1001/jamaoncol.2025.0985/). Collectively, these studies illustrate the evolving landscape of immunotherapy in lung cancer, highlighting the necessity for biomarker-driven strategies to optimize patient outcomes.

The integration of chemotherapy with immunotherapy has emerged as a pivotal strategy in the management of metastatic non-small cell lung cancer (NSCLC). Zhou et al. reported on the IMpower151 trial, which demonstrated that the combination of atezolizumab, bevacizumab, and chemotherapy significantly improved progression-free survival in chemotherapy-naive patients with metastatic nonsquamous NSCLC (ref: Zhou doi.org/10.1038/s41591-025-03658-y/). This trial highlights the importance of regional differences in treatment efficacy and the potential for combination therapies to enhance patient outcomes. Additionally, Lamberti et al. investigated the efficacy of carboplatin, etoposide, atezolizumab, and bevacizumab in the first-line treatment of extensive-stage SCLC, finding a promising signal of efficacy (ref: Lamberti doi.org/10.1136/jitc-2024-010694/). Moreover, novel therapeutic approaches are being explored, such as the development of CAR-T cell therapies for solid tumors. Osaki et al. optimized CAR-T cell therapy for solid tumors, while Zhang et al. demonstrated the synergistic effects of BCL-2 mutant B7H6-CAR-T cells combined with venetoclax in treating SCLC (ref: Zhang doi.org/10.1136/jitc-2024-010073/). These advancements in combination therapies and innovative treatment modalities reflect a growing understanding of the complexities of lung cancer and the need for multifaceted treatment strategies to improve patient outcomes.

Understanding the genetic and molecular mechanisms underlying lung cancer is crucial for developing targeted therapies. Esposito et al. investigated the role of AP1-mediated reprogramming of EGFR expression in RET-rearranged tumors, revealing that hyperactivation of the AP1 complex contributes to resistance against RET inhibitors (ref: Esposito doi.org/10.1186/s13046-025-03392-w/). This study underscores the importance of the EGFR signaling pathway in mediating drug resistance, suggesting that targeting this pathway may enhance treatment efficacy. In a related study, Miao et al. identified the long non-coding RNA LRTOR as a key driver of osimertinib resistance in EGFR-mutant NSCLC, correlating elevated LRTOR expression with poor prognosis in resistant patients (ref: Miao doi.org/10.1016/j.drup.2025.101245/). Additionally, Wang et al. highlighted the role of Retinoid X receptor γ (RXRγ) in driving chemoresistance in SCLC, suggesting that RXRγ could serve as a therapeutic target (ref: Wang doi.org/10.1073/pnas.2421199122/). These findings collectively emphasize the need for further exploration of genetic alterations and molecular pathways to inform the development of effective therapies for lung cancer.

The tumor microenvironment (TME) plays a critical role in the metastatic potential of lung cancer. Kawasaki et al. identified FOXA2 as a promoter of metastatic competence in SCLC, demonstrating that gene expression profiles can differentiate between patients with and without metastasis (ref: Kawasaki doi.org/10.1038/s41467-025-60141-5/). This study highlights the importance of understanding the molecular mechanisms that facilitate metastasis, which could lead to novel therapeutic strategies aimed at inhibiting metastatic progression. Furthermore, Murciano-Goroff et al. explored the responsiveness of different MET tumor alterations to type I and type II MET inhibitors, revealing that certain mutations confer resistance to specific inhibitors, thereby underscoring the necessity for personalized treatment approaches based on tumor genetics (ref: Murciano-Goroff doi.org/10.1002/ctm2.70338/). These insights into the TME and its interactions with tumor cells are essential for developing targeted therapies that can effectively combat metastasis and improve patient outcomes.

Clinical trials continue to provide valuable insights into the efficacy of lung cancer treatments, with real-world evidence complementing these findings. Felip et al. reported on the IMpower010 trial, which demonstrated that atezolizumab significantly improved disease-free survival in patients with resected stage IB-IIIA NSCLC following adjuvant chemotherapy (ref: Felip doi.org/10.1200/JCO-24-01681/). This study emphasizes the importance of long-term follow-up in assessing treatment outcomes and informs clinical decision-making. In addition, Sabari et al. conducted a cohort study analyzing overall survival in EGFR-mutant advanced NSCLC treated with osimertinib, revealing significant survival rates in high-risk subgroups (ref: Sabari doi.org/10.1016/j.jtho.2025.04.010/). The integration of clinical and biomarker data in real-world settings enhances our understanding of treatment responses and patient outcomes, ultimately guiding personalized treatment strategies for lung cancer patients.

Resistance mechanisms in lung cancer treatments pose significant challenges in achieving durable responses. Srivastava et al. developed a serum proteomic test to predict outcomes in advanced NSCLC patients treated with atezolizumab, demonstrating its prognostic value in stratifying patient responses (ref: Srivastava doi.org/10.1136/jitc-2024-010578/). This highlights the potential for biomarker-driven approaches to overcome resistance and improve treatment efficacy. Additionally, Xu et al. engineered pH-sensitive nanoparticles for the co-delivery of anti-PD-1 antibodies and MDK-siRNA, successfully overcoming immune checkpoint blockade resistance in hepatocellular carcinoma (ref: Xu doi.org/10.1186/s13046-025-03396-6/). The identification of novel resistance mechanisms, such as the role of long non-coding RNAs in osimertinib resistance, as reported by Miao et al., further emphasizes the complexity of resistance in lung cancer treatments (ref: Miao doi.org/10.1016/j.drup.2025.101245/). These studies collectively underscore the need for innovative strategies to address resistance and enhance treatment outcomes.

The landscape of lung cancer treatment is evolving with the introduction of novel therapeutic approaches. Ricciuti et al. evaluated the efficacy of neoadjuvant PD-1 and PD-L1 blockade combined with chemotherapy in stage III NSCLC, demonstrating improved surgical outcomes and pathological responses (ref: Ricciuti doi.org/10.1001/jamaoncol.2025.1115/). This study highlights the potential of combining immunotherapy with traditional chemotherapy to enhance treatment efficacy. Moreover, Wang et al. identified RXRγ as a therapeutic target in chemoresistant SCLC, suggesting that targeting this pathway could provide new avenues for treatment (ref: Wang doi.org/10.1073/pnas.2421199122/). Additionally, Cheng et al. explored the radiosensitizing effects of antiangiogenic drugs in single-dose radiotherapy, indicating that combining these approaches may improve treatment outcomes (ref: Cheng doi.org/10.1172/jci.insight.153601/). These advancements reflect a growing emphasis on innovative treatment strategies that integrate various therapeutic modalities to improve patient outcomes in lung cancer.

Assessing patient outcomes and quality of life is essential in lung cancer management. Iwsakul et al. conducted a simulation analysis of computed tomography scan intervals in real-world oncology studies, revealing significant variations in progression-free survival metrics (ref: Iwsakul doi.org/10.1016/j.jclinepi.2025.111841/). This study underscores the importance of accurate reporting and assessment of treatment responses in clinical practice. Furthermore, Grivas et al. reported on patient-reported outcomes from the JAVELIN Bladder 100 trial, demonstrating that avelumab maintenance therapy significantly prolonged overall survival without negatively impacting quality of life (ref: Grivas doi.org/10.1016/j.euo.2025.04.004/). Additionally, Passiglia et al. investigated the correlation between circulating tumor DNA variations and treatment outcomes in KRAS G12C-mutated NSCLC, highlighting the potential of ctDNA as a biomarker for monitoring treatment efficacy (ref: Passiglia doi.org/10.1002/cncr.35917/). These findings emphasize the need for a holistic approach to lung cancer treatment that prioritizes both clinical outcomes and patient quality of life.