mTOR inhibitor therapy as a disease modifying therapy for tuberous sclerosis complex

Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):365-373. doi: 10.1002/ajmg.c.31655. Epub 2018 Oct 11.


Between 1993 and 2003, through experiments involving Drosophila sp., cancer biologists identified the protein kinase known as the mammalian target of rapamycin, its pathway, and its relationship to the genes responsible for tuberous sclerosis. Thereafter, clinical research has resulted in regulatory approval of mTOR inhibitors for four distinct manifestations of the disease: giant cell astrocytoma, angiomyolipoma, lymphangioleiomyomatosis, and epilepsy. These developments are summarized and the practical use of mTOR inhibitors to improve the lives of patients with tuberous sclerosis reviewed.

Keywords: mTOR inhibition; neurogenetics; tuberous sclerosis.

Publication types

  • Review

MeSH terms

  • Angiomyolipoma / drug therapy
  • Angiomyolipoma / etiology
  • Clinical Trials as Topic
  • Epilepsy / drug therapy
  • Epilepsy / etiology
  • Humans
  • Lymphangiomyoma / drug therapy
  • Lymphangiomyoma / etiology
  • Mucositis / chemically induced
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use*
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis / drug therapy*
  • Tuberous Sclerosis / etiology


  • Protein Kinase Inhibitors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus