Biology-Driven Treatment Strategies in NSCLC: From Oncogene Addiction to Immunotherapy Integration

Non-Small Cell Lung Cancer (NSCLC) has undergone a profound transformation over the past two decades, evolving from a histology-driven to a biology-driven disease. The identification of actionable oncogenic drivers and the development of targeted therapies have significantly improved outcomes in selected patient populations. In parallel, the advent of immune checkpoint inhibitors has reshaped the therapeutic landscape across different disease stages.Despite these advances, several challenges remain. Treatment selection is increasingly complex and must account for tumor heterogeneity, co-occurring genomic alterations, and dynamic changes in tumor biology over time. The emergence of resistance mechanisms to both targeted therapies and immunotherapy further highlights the need for integrated and adaptive treatment strategies.This Research Topic aims to explore how a biology-driven approach can inform and optimize treatment decisions in NSCLC, bridging the gap between oncogene addiction and immune modulation. We welcome contributions addressing, but not limited to:• Integration and sequencing of targeted therapies and immunotherapy • Mechanisms of primary and acquired resistance • Role of co-mutations (e.g., TP53, STK11, KEAP1) in treatment outcomes • Minimal residual disease and circulating tumor DNA • Biomarker-driven patient selection • Perioperative and early-stage treatment strategies • Novel therapeutic approaches, including antibody-drug conjugates and bispecific agents • Real-world evidence and its role in guiding clinical decision-making By bringing together clinical, translational, and real-world perspectives, this Research Topic seeks to provide a comprehensive overview of the evolving treatment paradigms in NSCLC and to highlight future directions for precision oncology.Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Sarah Mazzilli, Andrea De Giglio Source: https://www.frontiersin.org/research-topics/84799/biology-driven-treatment-strategies-in-nsclc-from-oncogene-addiction-to-immunotherapy-integration