The immune microenvironment plays a crucial role in the response to immunotherapy in non-small cell lung cancer (NSCLC). A study utilizing single-cell RNA and TCR sequencing analyzed tumor samples from 234 NSCLC patients post-neoadjuvant chemo-immunotherapy, revealing significant immune heterogeneity that correlates with varying therapeutic outcomes (ref: Liu doi.org/10.1016/j.cell.2025.03.018/). Additionally, the phase III trial comparing subcutaneous and intravenous pembrolizumab in combination with chemotherapy demonstrated non-inferior pharmacokinetic exposure, suggesting that administration route may not significantly impact treatment efficacy (ref: Felip doi.org/10.1016/j.annonc.2025.03.012/). Mechanistically, IL-4 was found to downregulate TAP2, a critical component of the antigen presentation machinery, thereby facilitating immune evasion and resistance to immunotherapy (ref: Ranjan doi.org/10.1186/s12943-025-02276-z/). This highlights the complexity of the immune landscape in NSCLC and the need for tailored therapeutic strategies to overcome resistance. Furthermore, the gut microbiota has emerged as a potential biomarker for treatment outcomes, with specific genera linked to improved overall survival in patients receiving chemoimmunotherapy (ref: Hakozaki doi.org/10.1016/j.jtho.2025.02.026/). Overall, these findings underscore the intricate interplay between the immune microenvironment and therapeutic responses in NSCLC, necessitating further exploration of these dynamics to enhance treatment efficacy.

Targeted therapies in NSCLC have shown promise, particularly with the use of EGFR tyrosine kinase inhibitors (TKIs) like osimertinib. A study on molecular residual disease (MRD) following adjuvant osimertinib treatment indicated a significantly higher disease-free survival (DFS) rate compared to placebo, with an 86% event-free rate at 36 months (ref: Herbst doi.org/10.1038/s41591-025-03577-y/). Additionally, a phase 1 trial of a B7H3-targeting antibody-drug conjugate (ADC) demonstrated safety and preliminary efficacy in advanced solid tumors, indicating the potential of ADCs in targeted therapy (ref: Ma doi.org/10.1038/s41591-025-03600-2/). The role of tankyrase 2 (TNKS2) in NSCLC was highlighted as a driver of malignancy through apoptosis inhibition and enhanced cellular migration, positioning it as a promising therapeutic target (ref: Yu doi.org/10.5306/wjco.v16.i3.103234/). Furthermore, the combination of EGFR TKIs with chemotherapy has been explored, revealing no survival advantage but improved progression-free survival (PFS) with intercalated chemotherapy (ref: Kanda doi.org/10.1158/1078-0432.CCR-24-3532/). These studies collectively emphasize the evolving landscape of targeted therapies in NSCLC, highlighting the need for innovative approaches to overcome resistance and improve patient outcomes.

The identification of genetic and molecular biomarkers is pivotal in the management of lung cancer. A retrospective study on BRAF-V600 mutations in advanced NSCLC revealed significant prevalence and clinical outcomes, suggesting that genetic testing should be integrated into routine practice for personalized treatment strategies (ref: Jia doi.org/10.1016/j.ebiom.2025.105652/). Additionally, circulating tumor DNA (ctDNA) detection in early-stage NSCLC patients was associated with clinicopathological parameters, providing insights into tumor biology and potential prognostic indicators (ref: Driussi doi.org/10.1016/j.modpat.2025.100744/). The immunometabolite L-2-hydroxyglutarate (L-2-HG) was found to enhance antitumor immunity by promoting epigenetic modifications in exhausted T cells, indicating a novel metabolic pathway that could be targeted for therapeutic benefit (ref: Yang doi.org/10.1172/jci.insight.174600/). Furthermore, the role of PARP inhibitors in enhancing anti-PD-L1 immunotherapy through stabilization of chemokine mRNA was demonstrated, suggesting a synergistic approach to treatment (ref: Ran doi.org/10.1038/s41467-025-57257-z/). These findings highlight the importance of integrating genetic and molecular biomarkers into clinical practice to optimize treatment strategies and improve patient outcomes in lung cancer.

Chemotherapy remains a cornerstone in the treatment of advanced NSCLC, particularly in combination with targeted therapies. A network meta-analysis revealed that combination regimens, such as chemotherapy with anti-PD-1/PD-L1 agents, significantly prolonged progression-free survival (PFS) and improved overall response rates compared to standard chemotherapy alone (ref: Pang doi.org/10.6004/jnccn.2024.7092/). The efficacy of autologous cytokine-induced killer (CIK) cell therapy combined with toripalimab was also evaluated, showing promising results in improving PFS and overall survival in advanced NSCLC patients (ref: Zhong doi.org/10.1002/ijc.35422/). Additionally, aumolertinib combined with chemotherapy demonstrated a median PFS of 28 months, indicating its potential as a first-line treatment for patients with EGFR mutations (ref: Li doi.org/10.1093/oncolo/). However, the study on lorlatinib versus crizotinib highlighted the need for ongoing evaluation of treatment strategies, as lorlatinib showed a higher objective response rate in patients with baseline brain metastases (ref: Wu doi.org/10.1016/j.jtho.2025.02.021/). These findings underscore the importance of combination therapies in enhancing treatment efficacy and addressing resistance mechanisms in NSCLC.

Surgical interventions play a critical role in the management of lung cancer, particularly for early-stage disease. A study comparing anatomic lung resection to wedge resection for stage IA NSCLC found that lobectomy and segmentectomy were associated with improved overall survival (OS) and lung cancer-specific survival (LCSS) compared to wedge resection (ref: Seder doi.org/10.1016/j.jtho.2025.03.042/). This emphasizes the importance of surgical technique in optimizing patient outcomes. Additionally, the impact of external factors, such as exposure to wildfire disasters, was examined, revealing that patients exposed to such events had longer hospital stays following lung cancer surgery, highlighting the need for consideration of environmental factors in postoperative care (ref: Nogueira doi.org/10.1093/jnci/). Furthermore, the phase 2 results of trastuzumab rezetecan in HER2-mutant NSCLC demonstrated promising anti-tumor activity, suggesting that targeted therapies can complement surgical approaches (ref: Li doi.org/10.1016/S1470-2045(25)00012-9/). These findings collectively underscore the significance of surgical interventions and the need for a multidisciplinary approach to optimize treatment outcomes in lung cancer patients.

Understanding resistance mechanisms in lung cancer is crucial for developing effective therapies. A study identified NNMT as a promoter of acquired resistance to EGFR TKIs through feedback loops involving EGR1 and lactate, suggesting that targeting this pathway could enhance treatment efficacy (ref: Dai doi.org/10.1186/s12943-025-02285-y/). Additionally, CD105 blockade was shown to restore sensitivity to osimertinib in drug-resistant NSCLC, indicating a potential therapeutic strategy to overcome resistance (ref: Thiruvalluvan doi.org/10.1016/j.drup.2025.101237/). The role of Dickkopf-1 (DKK1) in mediating interactions between cancer cells and fibroblasts in gefitinib-resistant NSCLC was also highlighted, proposing DKK1 as a promising target for overcoming resistance (ref: Choi doi.org/10.1186/s40164-025-00616-9/). Furthermore, piperlongumine was found to overcome osimertinib resistance by modulating Sp1 turnover, suggesting that targeting specific molecular pathways may provide new avenues for treatment (ref: Wang doi.org/10.1172/jci.insight.186165/). These studies emphasize the complexity of resistance mechanisms in lung cancer and the need for innovative strategies to enhance therapeutic responses.

Clinical outcomes and quality of life (QOL) are critical considerations in lung cancer management. A study assessing QOL and neurocognitive functioning in patients surviving more than two years post-immune checkpoint inhibitor (ICI) treatment revealed significant psychological issues and comorbidities, highlighting the long-term impact of cancer treatment on survivors (ref: Candido doi.org/10.1136/jitc-2024-011168/). Additionally, the association between a germline polygenic risk score for autoimmune diseases and early ICI discontinuation due to immune-related adverse events (irAEs) was investigated, suggesting that genetic predispositions may influence treatment outcomes (ref: Middha doi.org/10.1136/jitc-2024-011273/). The role of PD-L1 signaling in driving immunosuppression through myeloid-derived suppressor cells was also examined, revealing potential targets for improving responses to ICIs (ref: Jeong doi.org/10.1136/jitc-2024-010612/). Furthermore, a multimodal nomogram incorporating tumor morphology and immune status was developed to predict adjuvant chemotherapy benefits in resectable lung adenocarcinoma, demonstrating the importance of personalized treatment approaches (ref: Lin doi.org/10.1136/jitc-2024-010723/). These findings underscore the need for comprehensive strategies to address both clinical outcomes and quality of life in lung cancer patients.

Emerging therapies and novel approaches are reshaping the landscape of lung cancer treatment. A study on the diagnostic accuracy of Total-Body PET/CT compared to conventional methods demonstrated high accuracy for nodal staging in NSCLC, suggesting advancements in imaging techniques could enhance diagnostic precision (ref: Mingels doi.org/10.1007/s00259-025-07177-3/). Additionally, the efficacy and safety of autologous CIK cell therapy combined with toripalimab were evaluated, showing significant improvements in progression-free survival and overall survival, indicating the potential of immunotherapy in combination with cellular therapies (ref: Zhong doi.org/10.1002/ijc.35422/). Furthermore, a novel pathway involving phosphorylated PKM2 in promoting stemness and chemoresistance was identified, highlighting the importance of metabolic regulation in cancer progression (ref: Wang doi.org/10.7150/thno.103722/). The inhibition of lipoylation was also found to enhance radiation control of lung cancer by suppressing homologous recombination DNA damage repair, suggesting metabolic targets could be leveraged for radiosensitization (ref: Chiang doi.org/10.1126/sciadv.adt1241/). These studies collectively emphasize the importance of integrating novel therapeutic strategies and emerging technologies to improve treatment outcomes in lung cancer.