Microbiome and -mutant non-small cell lung cancer: a complex interplay.

[INTRODUCTION] Epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC) exhibits unique biological and therapeutic characteristics. Although tyrosine kinase inhibitors (-TKIs) offer substantial clinical benefits, resistance development and treatment-related toxicities remain major challenges. Emerging evidence indicates that the host microbiome may significantly influence the efficacy and tolerability of -targeted therapies.

[AREAS COVERED] This review summarizes the main microbiome characteristics of -mutant NSCLC and discusses the interplay between gut, respiratory and intratumoral microbiome, and -TKI therapy in NSCLC, highlighting differential microbiome shifts associated with different TKIs and comparing the role of microbiome in modulating responses to -TKIs. The review also explores preclinical and early clinical strategies aimed at enhancing TKI efficacy and at, potentially, improving sensitivity of -mutant NSCLC to immunotherapy.

[EXPERT OPINION] Despite its emerging role, microbiome research in -mutant NSCLC holds substantial potential to refine therapeutic outcomes. Microbiota-targeted interventions may improve TKIs efficacy, mitigate toxicity, and potentially expand immunotherapeutic options in this molecularly and immunologically 'cold' subgroup. Future integrative studies combining microbiome, metabolome, and immune profiling are essential to translate these insights into personalized clinical strategies.