title: Everolimus tablets for patients with subependymal giant cell astrocytoma.
abstract: BACKGROUND
  Better understanding of aberrantly active molecular pathways in tumors offers potential to develop more specific and less toxic therapies. Abnormal mammalian target of rapamycin (mTOR) complex signaling and defects in TSC1 and TSC2 have been associated with the development of subependymal giant cell astrocytomas (SEGAs) in tuberous sclerosis complex (TSC) patients. Recently, mTOR inhibitors such as everolimus have shown encouraging benefit for patients with SEGAs.
  
  
  METHODS
  The authors discuss a molecular genetic pathway linked with TSC, specifically the role of two proteins whose functional absence is responsible for most SEGA tumors that arise in TSC patients. The authors also examine the rationale for targeted agents against this pathway therapeutically and describe the clinical evidence underlying the FDA approval of everolimus for patients with inoperable SEGAs.
  
  
  CONCLUSIONS
  Everolimus (Afinitor) selectively targets a molecular defect of SEGAs in TSC patients. Although surgery is effective, most SEGAs recur. An agent that inhibits an underlying molecular abnormality represents a particularly attractive therapeutic option for patients with inoperable or recurrent tumors. Studies are also underway to assess everolimus in treating other sequelae of TSC, and other gliomas. Finally, additional research aimed at better understanding aberrant cell signaling pathways may lead to the development of more effective therapeutics.
authors.affiliation: Duke University Medical Center, The Preston Robert Tisch Brain Tumor Center, Department of Surgery, Box 3624, Durham, NC 27710, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Turner
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Peters
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D000068338:Everolimus; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D011506:Proteins / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D013607:Tablets; D014402:Tuberous Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D011506:Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D013607:Tablets; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000068338:Everolimus; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus