Recent advancements in immunotherapy for lung cancer have focused on enhancing the efficacy of immune checkpoint inhibitors and understanding the tumor microenvironment. A study by Chen et al. introduced an innovative approach using oncolytic adenoviruses (OAs) delivered by T cells, engineered to express a Cas9 system targeting PD-L1, which could potentially overcome the limitations of traditional OA delivery methods (ref: Chen doi.org/10.1038/s41587-023-02118-7/). Nabet et al. explored immune heterogeneity in small-cell lung cancer (SCLC), identifying four distinct tumor subsets through transcriptomic analyses, which could inform combination therapy strategies with atezolizumab (ref: Nabet doi.org/10.1016/j.ccell.2024.01.010/). Besse et al. highlighted the challenges of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC), emphasizing the need for understanding mechanisms of resistance, such as defects in DNA damage response pathways (ref: Besse doi.org/10.1038/s41591-024-02808-y/). Furthermore, the ASCO living guidelines provided updated recommendations for treating stage IV NSCLC, addressing both patients with and without driver alterations, reflecting the evolving landscape of treatment options (ref: Jaiyesimi doi.org/10.1200/JCO.23.02746/; ref: Jaiyesimi doi.org/10.1200/JCO.23.02744/). Overall, these studies underscore the importance of personalized approaches in immunotherapy, considering tumor heterogeneity and resistance mechanisms.

The landscape of targeted therapies for lung cancer has expanded significantly, with a focus on overcoming resistance mechanisms and improving patient outcomes. Yu et al. reported on patritumab deruxtecan, an antibody-drug conjugate targeting HER3, which demonstrated promising overall survival in patients with EGFR-mutated NSCLC previously treated with EGFR TKIs (ref: Yu doi.org/10.1016/j.annonc.2024.02.003/). Gardner et al. investigated the lineage-specific intolerance to oncogenic drivers, revealing that lung adenocarcinoma can histologically transform into SCLC, highlighting the role of Myc as a critical driver in this process (ref: Gardner doi.org/10.1126/science.adj1415/). Additionally, Lee et al. introduced BI-4732, a novel EGFR inhibitor that showed remarkable efficacy against various EGFR mutations, including those associated with osimertinib resistance (ref: Lee doi.org/10.1158/1078-0432.CCR-23-2951/). Zheng et al. provided updated survival data on ensartinib for crizotinib-refractory ALK-positive NSCLC, reinforcing its clinical activity (ref: Zheng doi.org/10.1002/cac2.12524/). These findings collectively emphasize the need for continuous innovation in targeted therapies to address resistance and improve survival rates in lung cancer patients.

Genomic testing and biomarker research are critical in advancing personalized medicine for lung cancer. Meernik et al. conducted a systematic review revealing significant racial and ethnic disparities in genomic testing among lung cancer patients, which may affect access to precision therapies (ref: Meernik doi.org/10.1093/jnci/). Jiang et al. explored a biomimetic proteinoid that enhances immunotherapy efficacy in lung adenocarcinoma, demonstrating its potential to reactivate antitumor immune responses (ref: Jiang doi.org/10.1021/acsnano.3c09852/). Sun et al. reported on the efficacy of neoadjuvant sintilimab combined with chemotherapy, achieving high disease control rates and significant downstaging in stage IIIA/IIIB NSCLC (ref: Sun doi.org/10.1016/j.eclinm.2024.102422/). Furthermore, Zhang et al. highlighted the role of ubiquitin-specific peptidase 38 in lung adenocarcinoma progression, linking its expression to poor prognosis (ref: Zhang doi.org/10.1038/s41388-024-02985-7/). These studies illustrate the importance of integrating genomic insights into clinical practice to enhance treatment strategies and outcomes for lung cancer patients.

The tumor microenvironment (TME) plays a pivotal role in lung cancer progression and metastasis. Li et al. identified UPP1 as a promoter of lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment, utilizing single-cell RNA sequencing to analyze patient samples (ref: Li doi.org/10.1038/s41467-024-45340-w/). Papavassiliou et al. examined cancer-associated fibroblast (CAF) heterogeneity in NSCLC, revealing distinct CAF phenotypes associated with prognosis and metastasis, emphasizing the spatial relationship between CAFs and immune cell infiltration (ref: Papavassiliou doi.org/10.1016/j.trecan.2024.02.004/). Jin et al. investigated the role of the farnesoid X receptor in promoting NSCLC metastasis via Jak2/STAT3 signaling, highlighting its potential as a therapeutic target (ref: Jin doi.org/10.1038/s41419-024-06495-y/). These findings underscore the complexity of the TME in lung cancer and the need for targeted strategies to modulate it for therapeutic benefit.

Clinical trials and treatment guidelines are essential for establishing effective management strategies for lung cancer. The ASCO living guidelines provided updated recommendations for stage IV NSCLC, addressing treatment options for patients with and without driver alterations, reflecting the dynamic nature of clinical practice (ref: Jaiyesimi doi.org/10.1200/JCO.23.02746/; ref: Jaiyesimi doi.org/10.1200/JCO.23.02744/). Pal Choudhuri et al. reported on acquired cross-resistance in SCLC due to MYC paralog amplification, emphasizing the need for ongoing research into resistance mechanisms (ref: Pal Choudhuri doi.org/10.1158/2159-8290.CD-23-0656/). Additionally, Lee et al. demonstrated the efficacy of a novel EGFR inhibitor against various mutations, reinforcing the importance of targeted therapies in clinical settings (ref: Lee doi.org/10.1158/1078-0432.CCR-23-2951/). These studies collectively highlight the importance of clinical trials in shaping treatment guidelines and improving patient outcomes in lung cancer.

Understanding epidemiology and risk factors is crucial for lung cancer prevention and management. Mochizuki et al. investigated the mutagenic effects of passive smoking in lung adenocarcinoma, revealing its significant role as a carcinogen, particularly among never-smokers (ref: Mochizuki doi.org/10.1016/j.jtho.2024.02.006/). Shibaki et al. developed a machine learning model to predict immunotherapy efficacy in SCLC based on the tumor immune microenvironment, highlighting the potential for personalized treatment approaches (ref: Shibaki doi.org/10.1136/jitc-2023-007987/). Lin et al. assessed the impact of pre-CCRT PET-CT staging on survival in unresectable EGFR mutation-positive adenocarcinoma, demonstrating improved outcomes with this staging method (ref: Lin doi.org/10.1136/thorax-2023-220702/). These findings underscore the importance of identifying risk factors and utilizing advanced technologies to enhance lung cancer management.

Research into histological and molecular subtypes of lung cancer is vital for tailoring treatment strategies. Xie et al. utilized spatial transcriptomics to reveal heterogeneity between lepidic and acinar subtypes of lung adenocarcinoma, providing insights into their distinct prognoses (ref: Xie doi.org/10.1002/ctm2.1573/). Gardner et al. discussed the lineage-specific intolerance to oncogenic drivers, which restricts the transformation of lung adenocarcinoma into SCLC, implicating Myc as a key factor in this process (ref: Gardner doi.org/10.1126/science.adj1415/). Zhang et al. highlighted the role of ubiquitin-specific peptidase 38 in lung adenocarcinoma progression, linking its expression to poor patient outcomes (ref: Zhang doi.org/10.1038/s41388-024-02985-7/). These studies emphasize the need for a deeper understanding of histological and molecular characteristics to improve prognostic assessments and treatment decisions in lung cancer.