Tuberous sclerosis complex (TSC) is a genetic multiple organ system disorder that is characterized by the
development of tumor-like lesions (hamartomas) and neurodevelopmental disorders. Mutations in the TSC1 and TSC2
tumor suppressor genes occur in the majority of patients with TSC, resulting in hyperactivation of the mammalian target
of rapamycin (mTOR) signaling pathway and subsequent abnormalities in numerous cell processes. As a result, mTOR
inhibitors such as sirolimus and everolimus have the potential to provide targeted therapy for patients with TSC.
Everolimus is the first mTOR inhibitor approved as a treatment option in the USA and in Europe for patients with
subependymal giant-cell astrocytomas (SEGAs) associated with TSC. The clinical evidence to date supports the use of
mTOR inhibitors in a variety of TSC-associated disease manifestations, including SEGAs, renal angiomyolipoma, skin
manifestations, and epilepsy. Furthermore, ongoing clinical trials evaluating mTOR inhibitors in TSC are underway, and
the results of these studies are expected to provide further evidence that will firmly establish their role in this setting. This
article will discuss the role of the mTOR pathway in TSC and review the pharmacokinetics, pharmacodynamics, clinical
efficacy, and tolerability of mTOR inhibitors, along with their current place in clinical practice.
Keywords: Angiomyolipoma, tuberous sclerosis complex, everolimus, mTOR inhibition, subependymal giant cell astrocytoma,
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