[Everolimus (RAD001) and solid tumours: a 2008 summary].
Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a mediator in the downstream signalling pathway phosphatidylinositol 3-kinase/Akt, playing a key role in regulation of basic cellular functions including growth and cell proliferation. The inhibitor of mTOR RAD001, or everolimus (Novartis Pharma AG), is a hydroxyethyl ether rapamycin derivative administered orally. Everolimus showed an important anti-angiogenic and antiproliferative activity on cell lines derived from human tumours and on xenograft models of human tumours. This molecule appears well tolerated, with skin reactions, stomatitis, myelosupression and metabolic abnormalities transient and reversible with interruption of treatment. Clear data suggest antitumor activity, including tumour regression and prolonged stable disease, which has been reported in patients with a variety of malignancies, especially those with metastatic renal cell cancer. Here, we review the preclinical data of this compound with current clinical results and future developments.
Lévy
A
A
Département de médecine, service des innovations thérapeutiques précoces (SITEP), Institut Gustave-Roussy, Villejuif.
Sauvin
L Albiges
LA
Massard
C
C
Soria
J-C
JC
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000068338:Everolimus; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus