Despite the impressive clinical efficacy,MM remains fatal due to the development of drug resistance over time.During MM progression, stress responses to hypoxia and PIs suppressmammalian target of rapamycin complex 1 (mTORC1) activity by releasingtuberous sclerosis complex 2 (TSC2), which deactivates Ras homologueenriched in brain (Rheb), a crucial regulator of mTORC1. This evidence concerns the gene RHEB and Miyoshi myopathy.