Precision Medicine in Oncology Drug Development

Abstract

Overview In recent years, advances in technology have led to identification of complex and unique biologic mechanisms of tumorigenesis. Precision medicine uses tumor and cell‐free DNA profiling, immune markers, RNA and proteomic analyses, and other biomarkers in combination with patients' unique characteristics and comorbidities to individualize anticancer therapy. The focus of selected clinical trials has shifted from tumor type‐centered to gene‐directed, and in some cases, histology‐agnostic approaches. Innovative trial designs tailored to biomarker profiling aim to improve treatment outcomes. These designs enable the dynamic evolution of the studies, allow the elimination of treatment arms with inferior outcomes and modification of patient randomization, and optimize biomarker selection based on real‐time study outcomes. They also accelerate regulatory approval of novel drugs by empowering seamless transition from phase I to phase II and III clinical trials. Companion diagnostic biomarkers provide essential information for the safe and effective use of the corresponding targeted or immune treatments and lead to improved clinical outcomes of patients with molecular alterations treated with matched targeted treatments. However, the complex interaction between tumors, immune cells, and the tumor microenvironment complicates the identification of robust biomarkers. To overcome biologic complexity and tumor heterogeneity, clinical trials evaluate combinations of gene‐targeted therapy with immune‐targeted approaches (e.g., checkpoint blockade, personalized vaccines, oncolytic viruses, and/or adoptive cell therapy), hormonal therapy, chemotherapy, and/or novel agents, customized to individuals in an N‐of‐1 fashion. In this article, we discuss the rapid evolution of precision medicine in oncology and the challenges and opportunities associated with its implementation into daily clinical practice.