Lessons learned from exceptional responders

Abstract

ABSTRACT Introduction: Since the advent of anti-cancer therapies, physicians have observed that certain patients experience deep, durable responses to these agents (exceptional responders). The application of next-generation sequencing methodologies to these responders has revealed in many cases novel predictive biomarkers of drug sensitivity and could result in the salvage of drugs that would otherwise be considered ineffective as anti-cancer agents. Areas covered: This review provides select examples of exceptional response analyses and the ramifications of these analyses upon biomarker selection and clinical trial design within the context of precision medicine. A literature search for ‘exceptional responder’ AND ‘targeted therapy’, ‘chemotherapy,’ or ‘immunotherapy’ was performed in PubMed to identify articles of interest. Expert opinion: Exceptional responses represent an invaluable tool to better understand the biology of genomic alterations in specific cancers and to identify predictive biomarkers of response. The National Cancer Institute has acquired tissue from exceptional responders across tumor types for detailed genomic analysis. These patient tumors must be mined using available technology to help define populations most likely to respond to specific therapies.