The enigma of rapamycin dosage Journal Article

Authors: Mukhopadhyay, S.; Frias, M. A.; Chatterjee, A.; Yellen, P.; Foster, D. A.
Article Title: The enigma of rapamycin dosage
Abstract: The mTOR pathway is a critical regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling has been observed in most cancers and, thus, the mTOR pathway has been extensively studied for therapeutic intervention. Rapamycin is a natural product that inhibits mTOR with high specificity. However, its efficacy varies by dose in several contexts. First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of differentmTORsubstrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Rapamycin and PA have opposite effects on mTOR whereby rapamycin destabilizes and PA stabilizes bothmTORcomplexes. In this review, we discuss the properties of rapamycin dosage in the context of anticancer therapeutics. © 2016 American Association for Cancer Research.
Journal Title: Molecular Cancer Therapeutics
Volume: 15
Issue: 3
ISSN: 1535-7163
Publisher: American Association for Cancer Research  
Date Published: 2016-03-01
Start Page: 347
End Page: 353
Language: English
DOI: 10.1158/1535-7163.mct-15-0720
PROVIDER: scopus
PMCID: PMC4783198
PUBMED: 26916116
Notes: Review -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Paige Blanche Yellen
    2 Yellen