Dr. Ho on How Molecular Subtypes Affect Sequencing

Thai H. Ho, MD, PhD, assistant professor of medicine, Mayo Clinic, discusses common molecular subtype and phenotype alterations in the epigenetic pathway that are used to predict response to treatment.

Molecular subtypes from the thermogravimetric analysis show that there are certain mutations that are recurrent in renal cell carcinoma; these include VHL, which is the most common mutation, followed by PBRM1, BAP1, and SETD2. Certain types of epigenetic mutations are associated with a favorable response to immune therapy and are currently being studied.

There are also molecular phenotypes that are defined by poor and intermediate risk. These are phenotypes that can be defined based on routine lab work. The patients who were defined as poor and intermediate risk were the patients who were enriched in the CABOSUN study, which led to the approval of cabozantinib. Similarly, these patients were studied in the CheckMate-214 trial, and showed an improved response in combination with nivolumab (Opdivo) and ipilimumab (Yervoy).