Lung Cancer: A Comprehensive Review of Etiopathogenesis, Molecular Stratification, and the Paradigm Shift in Precision Oncology

Abstract

Lung cancer remains the preeminent global oncologic challenge, maintaining its status as the leading cause of cancer-related mortality alongside a significant epidemiological shift toward developing nations. This comprehensive review explores the complex etiopathogenesis of the disease, highlighting the interplay between tobacco-induced epigenetic modifications and chronic inflammation within the tumor microenvironment. The article details the evolution of pathological classification, specifically the transition toward standardized TNM staging for Small Cell Lung Cancer (SCLC) to guide increasingly complex multimodal care.
A major focus is placed on the paradigm shift in Non-Small Cell Lung Cancer (NSCLC), where molecular profiling has transformed from an advanced-stage necessity to an early-stage imperative. The review analyzes the impact of landmark trials, such as ADAURA and ALINA, which established the efficacy of adjuvant targeted therapies. Furthermore, it examines the expanding landscape of actionable genomic drivers—including EGFR, ALK, and the historically undruggable KRAS G12C—and the strategies utilized to overcome acquired resistance. Finally, the author discusses emerging therapeutic frontiers, including the rise of Antibody-Drug Conjugates (ADCs), the potential of Personalized Cancer Vaccines (PCVs) for eliminating minimal residual disease, and the clinical utility of liquid biopsy (ctDNA) for dynamic tumor profiling.