Mammalian target of rapamycin as a therapeutic target in oncology.
BACKGROUND
The mammalian target of rapamycin (mTOR) has emerged as a validated therapeutic target in cancer and mTOR inhibitors alter tumor cell responses to mitogenic signals and microenvironmental stress.


OBJECTIVE
The aims of this review are to describe the mTOR signaling pathway and the rationale for the use of rapamycin analogs and other mTOR inhibitors for oncology indications.


METHODS
This review presents information from recent publications, as well as some more conjectural viewpoints stemming from the early clinical experience with mTOR inhibitors in cancer patients.


CONCLUSIONS
A thorough understanding of the antitumor mechanisms of the existing mTOR inhibitors will drive the development of effective combination therapies to overcome tumor resistance to these agents. Furthermore, the development of second-generation inhibitors of this critical protein target may yield deeper and broader therapeutic activities in human cancers.
Abraham
Robert T
RT
Oncology Discovery Research, Wyeth, 401 N. Middletown Road, Pearl River, NY 10965, USA. abrahar@wyeth.com
Eng
Christina H
CH
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases