Role of Heterogeneity in Lung Cancer and its Implications for Personalized Oncology

Tumor heterogeneity represents a major biological barrier to effective cancer treatment, arising from complex and dynamic interactions between genetic alterations, epigenetic regulation, and the tumor microenvironment.In lung cancer, which includes non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), this diversity is expressed across spatial and temporal dimensions, driving clonal evolution, therapeutic resistance, and disease progression.This review consolidates current evidence on the molecular and non-molecular mechanisms that generate heterogeneity in lung cancer, with particular emphasis on genomic instability, somatic mutation patterns, epigenetic plasticity, and immune interactions within the tumor microenvironment.We discuss how heterogeneity manifests differently in NSCLC and SCLC, highlighting subtype-specific cell states, immune escape mechanisms, and lineage plasticity.The clinical implications for personalized oncology are substantial, influencing both targeted therapy and immunotherapy outcomes.Despite advances in multiomics profiling, challenges remain in accurately capturing heterogeneity and translating these insights into durable clinical benefit.Emerging approaches including single-cell technologies, spatial profiling, and adaptive therapeutic strategies offer promising avenues to address these challenges and improve individualized treatment outcomes for patients with lung cancer.