Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.

Non-small cell lung cancer (NSCLC) is characterized by intricate genetic modifications and mechanisms that allow it to evade immune detection, which complicates the pursuit of lasting therapeutic responses. The effectiveness of treatments is greatly affected by the interaction between tumor genetic profiles and the surrounding immune microenvironment, highlighting the need for carefully designed therapeutic combinations. This review provides a comprehensive analysis of oncogenic drivers and signaling pathways (such as the KRAS, BRAF, and CD73/adenosine pathway) that interact with immune checkpoint inhibitors (ICIs), offering practical insights for personalized treatment approaches. The key findings focus on the use of biomarkers to guide the selection of immunotherapy or ICI-based combination therapies (e.g., ICIs plus tyrosine kinase inhibitors or signaling pathway inhibitors). We emphasize the importance of integrating tumor genomics with immune profiling to improve patient survival outcomes. This review aims to optimize treatment strategies by synthesizing insights from recent clinical trials and preclinical research, ultimately improving therapeutic efficacy in NSCLC.