The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and targeted antitumour therapy.
The mammalian target of rapamycin (mTOR) is a kinase responsible for mitogen-induced cell proliferation/survival signaling. Its activation in response to mitogens leads to a cell-cycle progression from G1 to S phase. mTOR controls the activation of ribosomal protein translation and the initiation of cap-dependent translation. A role of mTOR signaling pathway dysregulation in tumourigenesis is postulated. mTOR and pathways upstream of this kinase were found to be frequently upregulated in neoplastic diseases. Therefore, it is also an attractive target for antitumour therapy. Several mTOR inhibitors were developed, including rapamycin and its analogues: CCI-779, RAD001 and AP23573. After promising phase I studies, their potential clinical significance is currently under evaluation in several phase II-III trials on patients with solid tumours and some hematological malignancies.
Janus
Agnieszka
A
Department of Hematology, Medical University of Łódź, Copernicus Memorial Hospital, Ciołkowskiego 2, 93-510 Łódź, Poland.
Robak
Tadeusz
T
Smolewski
Piotr
P
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism / Q000627:therapeutic use*; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus