Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex

Figure 1

Overview of mTOR-TSC regulation and upstream and downstream mediators. Both TSC1 and TSC2 are major components in mTOR signalling cascade. mTOR complexes 1 and 2 (mTORC1 and mTORC2, resp.) are mediators of important cellular functions: mTORC1 (which senses nutrients, energy, growth factors, and stress signals) promotes protein synthesis, cell growth, and cell proliferation, while mTORC2 is associated with cell survival and proliferation. Tuberous sclerosis complex patients present mutations in either TSC1 or TSC2 genes, causing suppression of RHEB-mediated mTORC1 inhibition, exacerbating cell cycle progression, cell proliferation, and growth. Rapamycin (sirolimus) and everolimus are effective inhibitors of mTORC1 via FKBP12.