Through elucidating the genetic mechanisms of drug sensitivity, precision medicine aims to improve patient selection and response to therapy. Exceptional responders are patients that exhibit exquisite and durable responses to targeted therapy, providing a rare opportunity to identify the molecular basis of drug sensitivity. We identified an exceptional responder to everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR) pathway, in a patient with advanced renal cell carcinoma. Through whole-exome sequencing on pretreatment and metastatic tumor DNA, we identified alterations in several mTOR pathway genes, with several mutations implicated in mTOR activation. Importantly, these alterations are currently not included in commercially available next-generation sequencing panels, suggesting that precision medicine is still limited in its ability to predict responses to mTOR-targeted therapies. Further research to discover and validate predictive biomarkers of response to everolimus and other targeted therapies is urgently needed. Given the rarity of patients with exceptional responses to targeted agents, cooperative efforts to understand the molecular basis for these phenotypes are essential.
Case reports in oncology. 2021 Aug 16*** epublish ***
Amanda Pilling, Christopher Wee, Eliezer Bar-Meir, Gregory Dyson, Ok Hwang, Nilesh Gupta, Dhananjay Chitale, Clara Hwang
Department of Internal Medicine, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, Michigan, USA., Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA., Department of Oncology, Population Statistics, Wayne State University School of Medicine, Detroit, Michigan, USA., Department of Pathology, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, Michigan, USA.