Lung adenocarcinoma is the most common subtype of non small cell lung cancer and arises from gland forming cells in the lung. It frequently occurs in the lung periphery and is now increasingly diagnosed in never smokers, especially women, although tobacco smoking remains a major risk factor. Additional risks include air pollution, occupational exposures, prior lung disease and genetic susceptibility.

Genetically, lung adenocarcinoma is driven by recurrent oncogenic alterations that activate growth and survival pathways. Key actionable mutations include EGFR, ALK rearrangements, ROS1 fusions, BRAF V600E, MET exon 14 skipping, RET fusions, NTRK fusions and KRAS variants, particularly KRAS G12C. These drivers are usually mutually exclusive and define biologically distinct subgroups. Many tumors also harbor co occurring alterations that influence prognosis and treatment response.

Pathologically, tumors range from preinvasive atypical adenomatous hyperplasia and adenocarcinoma in situ through minimally invasive to frankly invasive forms. Molecular changes, such as EGFR mutations and KRAS mutations, often appear early in this progression.

Targeted therapies directed at specific driver mutations have transformed outcomes for many patients. EGFR and ALK inhibitors, as well as agents targeting ROS1, BRAF, MET, RET, NTRK and KRAS G12C, can produce substantial and sometimes prolonged responses. However, resistance commonly develops through secondary mutations, bypass pathway activation or histologic transformation, prompting sequential treatment strategies and combination approaches.

Immune checkpoint inhibitors benefit subsets of patients, particularly those whose tumors lack targetable drivers and have high PD L1 expression or high tumor mutational burden. Current research focuses on overcoming resistance, expanding the range of targetable alterations and integrating molecular profiling into early stage disease management.