Pulmonary Enteric Adenocarcinoma: From Diagnostic Attribution and Molecular Biology to Biomarker-Guided Clinical Pharmacology

Background/Objectives: Pulmonary enteric adenocarcinoma (PEAC) is a rare lung tumor with intestinal differentiation and marked overlap with metastatic colorectal adenocarcinoma. Misclassification can substantially alter therapeutic decisions. This review integrates contemporary diagnostic, molecular and treatment evidence with an emphasis on clinical pharmacology. Methods: In this narrative review, we critically appraised major classification documents, primary clinicopathologic studies, comparative genomic analyses, contemporary PEAC molecular cohorts, pooled outcome reports and landmark biomarker-defined non-small-cell lung cancer (NSCLC) trials published through September 2026; supplementary pharmacology and trial-record verification was performed in October 2026. Results: Accurate attribution requires coordinated gastrointestinal evaluation, morphology and a panel of pulmonary and enteric markers; paired sequencing or methylation profiling may help in selected cases. KRAS and TP53 are recurrent alterations, while uncommon EGFR, ERBB2 and kinase-fusion events can inform biomarker-matched treatment. Reported immune features are heterogeneous, and mismatch-repair gene alterations should not be conflated with confirmed microsatellite instability. A pooled analysis of 127 patients (126 published) reported a median overall survival of 14 months in advanced/metastatic disease but did not establish comparative treatment efficacy. Drug interactions, CNS activity and treatment-related lung injury require attention; non-G12C RAS inhibitors remain unvalidated in PEAC. Conclusions: Stage IV management should follow molecularly appropriate NSCLC principles while carefully distinguishing directly observed PEAC evidence from extrapolated trial data. Multicenter registries and prospective molecularly annotated studies are urgently needed.