FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes. mTOR is one of the substrates of FBXW7-mediated protein degradation, and loss of function of FBXW7 increases the levels of total and activated mTOR. Due to the disruption of the WD repeat domain, the FBXW7 R393* truncating mutation is predicted to lead to a loss of FBXW7 protein function. Preclinical data have suggested that inactivating mutations of FBXW7 could predict sensitivity to the mTOR inhibitor rapamycin; however, the clinical utility remains unknown. A single study has reported only limited activity in phase I trials using mTOR inhibitors in patient with advanced cancers including colorectal cancer.