Precision Medicine in Oncology: A Review of Multi-Tumor Actionable Molecular Targets with an Emphasis on Non-Small Cell Lung Cancer

Abstract

Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, NTRK) and on those alterations with approvals in multiple malignancies (BRAF, ERBB2, RET, BRCA, PD-L1), we also describe several biomarkers or indications that are likely to lead to an approved drug in the near future (e.g., KRAS G12C, PD-L1 amplification, HER2 overexpression in colon cancer, HER2 mutations in lung cancer). Finally, we detail the current landscape of additional actionable alterations (EGFR, ALK, ROS1, MET) in lung cancer, a biomarker-rich malignancy that has greatly benefitted from the precision oncology revolution.