non-small cell lung cancer

Non-small cell lung cancer (non small cell lung cancer) is a major lung cancer subtype and a common setting for precision oncology, immunotherapy, and biomarker-driven treatment selection. It is especially studied in advanced, metastatic, and unresectable stage III disease, including EGFR-mutated tumors, where outcomes such as overall survival, progression-free survival, objective response rate, disease control rate, and treatment-related adverse events are tracked. Mechanistically, the disease is shaped by tumor microenvironment effects, TP53 dysfunction, and resistance biology, while predictive biomarker testing and multi-omics approaches are being used to refine therapy. Recent advances include AI-based immunotherapy response prediction, multi-omics biomarker discovery, and ADC target profiling, alongside clinical development of agents such as osimertinib, rezivertinib, nivolumab, atezolizumab, amivantamab, adagrasib, and sotorasib. The literature also highlights emerging strategies such as pre-operative PD-1 blockade with RANKL inhibition, bronchoscopic cryoimmunotherapy, cryoablation, and pyroptosis-inducing nanomedicines for apoptosis-resistant disease. Biomarkers including b7 h3-enriched exosomes and B-cell/tertiary lymphoid structure signatures are being explored for diagnosis, prognosis, and response prediction.

Advanced / EGFR-mutated disease

• In advanced or metastatic EGFR-mutated NSCLC, treatment-naïve patients were analyzed for systemic and CNS efficacy, including those with baseline CNS metastases. (PMID:41924561)
• rezivertinib was tested as first-line therapy in EGFR-mutated NSCLC, and a phase III REZOR study reported CNS efficacy in patients with CNS metastasis. (PMID:41924561)
• osimertinib is described as a primary treatment for EGFR-mutated NSCLC. (PMID:41920265)
• gefitinib served as a comparator in advanced EGFR-mutated NSCLC, reflecting ongoing sequencing of EGFR-targeted therapy. (PMID:41730505)

Immunotherapy / perioperative management

• A retrospective study in unresectable stage III NSCLC compared induction chemoimmunotherapy followed by radiotherapy and consolidation immunotherapy versus definitive concurrent chemoradiotherapy with consolidation immunotherapy. (PMID:41200891)
• The POPCORN phase 1b/2 trial evaluated pre-operative PD-1 blockade plus RANKL inhibition in NSCLC. (PMID:41957527)
• A Colombian Delphi consensus addressed perioperative and locally advanced NSCLC management, emphasizing real-world treatment pathways. (PMID:41921504)
• Neoadjuvant immunotherapy efficacy in resectable NSCLC was assessed using machine learning models in a systematic review and meta-analysis. (PMID:41719848)

Biomarkers / AI / tumor biology

• Multi-omics and AI approaches are being used to predict immunotherapy efficacy in NSCLC and to discover biomarkers through data-driven network methods. (PMID:41867453) (PMID:41937706)
• b7 h3-enriched exosomes were highlighted as promising diagnostic, prognostic, and predictive biomarkers in NSCLC. (PMID:41964005)
• ADC target profiling in NSCLC used generalizable AI to separate TROP-2 and cMET phenotypes, supporting biomarker-guided drug selection. (PMID:41945491)
• Baseline vitamin D status was examined in advanced NSCLC patients treated with nivolumab, linking host factors to clinical outcomes. (PMID:41981174)

Novel therapies / resistance mechanisms

• amivantamab plus chemotherapy was described as a novel combination strategy in NSCLC. (PMID:41945491)
• atezolizumab was reviewed in a subcutaneous formulation for NSCLC treatment, expanding delivery options. (PMID:41946650)
• cryoablation and bronchoscopic cryoimmunotherapy were reviewed as therapeutic approaches, including combinations with immune checkpoint inhibitors. (PMID:41989053)
• gamabufotalin suppressed NSCLC cell proliferation and tumor growth in cell and xenograft models by inhibiting CHCHD2 and modulating XAF1. (PMID:41692347)
• pyroptosis inducing nanomedicines were proposed as a dual-mode framework for apoptosis-resistant lung cancer, relevant to NSCLC resistance biology. (PMID:41655514)

Immunology / microenvironment

• The NSCLC tumor microenvironment was described as central to progression, immune evasion, and immunotherapy resistance. (PMID:41958218) (PMID:41759799)
• Exosome-mediated crosstalk between immune cells and the tumor microenvironment was linked to immune evasion and therapeutic resistance in lung cancer. (PMID:41759799)
• B-cell signatures and tertiary lymphoid structures were associated with complete pathologic response to perioperative chemoimmunotherapy in NSCLC. (PMID:41805895)
• Anti-PD-1 responding cases showed downregulation of Mettl8 and TCF7, suggesting immune-state remodeling in responders. (PMID:41891923)

Modeling / translational methods

• Classical tumor growth inhibition models were evaluated using clinical trial data from NSCLC patients, supporting quantitative treatment-response modeling. (PMID:41919988)
• A multi-omics, data-driven network approach using the U-centered Distance Correlation Network was applied to biomarker discovery in NSCLC. (PMID:41937706)
• Artificial intelligence was also used to predict immunotherapy efficacy in NSCLC, reflecting rapid adoption of computational oncology tools. (PMID:41867453)
• Predictive biomarker testing was emphasized to tailor therapy and address drug resistance in NSCLC. (PMID:41945491)