Targeted therapy for tuberous sclerosis complex

The tuberous sclerosis complex genes (TSC1 and TSC2) function as classic tumor suppressor genes in health; a loss of function of these genes results in activation of the kinase m-TOR and to development of benign tumors. Despite their slow progression, renal subependymal giant cell astrocytomas and angiomyolipomas can cause fatal outcomes. Both Phases I–II and III EXIST-1 and EXIST-2 trials demonstrated that the m-TOR inhibitor everolimus had good efficacy and tolerability: the volume of astrocytomas and that of angomyolipomas were reduced by 50% or more in 35 and 41% of patients, respectively. After 3.5 years of the trials, everolimus showed a high retention rate: 80.2 and 79% of the patients, respectively. Virtually all patients were observed to have adverse reactions, most commonly stomatitis, oral ulcers, and nasopharyngitis. Everolimus has been registered in the Russian Federation and Russian patients participated in the EXIST-1 and EXIST-2 trials. The indications for prescribing the drug are tuberous sclerosis complex-associated subependymal giant cell astrocytomas and angomyolipomas in patients older than 3 and in those older than 18 years of age, respectively. Everolimus has the potential for targeted treatment for the spectrum of clinical manifestations of tuberous sclerosis complex. 

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