However, rapalogs have shown limited benefit in treating patients with RCC, bladder cancer (BLCA), and cancers of any origin with biallelic mutations in either TSC1 or TSC2 (11–13), which may be due to the incomplete suppression of mTORC1 kinase activity by rapalogs, including a lack of effect on p-4EBP1T37,46, p-PRAS40S183, and p-Grb10S150 (14). This evidence concerns the gene TSC1 and renal cell carcinoma.