Precision Oncology Medicine: The Clinical Relevance of Patient‐Specific Biomarkers Used to Optimize Cancer Treatment

Precision medicine in oncology is the result of an increasing awareness of patient‐specific clinical features coupled with the development of genomic‐based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug‐target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA‐approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug‐metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression‐based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next‐generation sequencing to detect many potential “actionable” cancer molecular alterations is further shifting the 1 gene–1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI‐MATCH, NCI‐MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI‐MATCH will help determine the clinical utility and future development of the precision‐medicine approach.