The emerging safety profile of mTOR inhibitors, a novel class of anticancer agents.
Mammalian target of rapamycin (mTOR) has emerged as an important target for cancer therapy. Rapamycin has a distinct, well-documented toxicity profile and most of the toxicity data has been reported in patients with organ transplantation. Newer mTOR inhibitors have slightly different pharmacokinetic properties, yet they present toxicity profiles similar to rapamycin. Most of these toxicities are mild to moderate in severity and can be managed clinically by dose modification and supportive measures. Mucositis and pneumonitis are the most commonly reported toxicities, but they rarely lead to treatment discontinuation. Pathogenesis of pneumonitis is uncertain, but various hypotheses have been suggested, including cell-mediated immune response to the drug.
Sankhala
Kamalesh
K
Institute for Drug Development, Cancer Therapy and Research Center at the University of Texas Health Science Center, San Antonio, TX 78229, USA.
Mita
Alain
A
Kelly
Kevin
K
Mahalingam
Devalingam
D
Giles
Francis
F
Mita
Monica
M
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000276:immunology*; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D052016:Mucositis / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016377:Organ Transplantation; D011014:Pneumonia / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism*; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus