Toward rapamycin analog (rapalog)-based precision cancer therapy

Rapamycin and its analogs (rapalogs) are the first generation of mTOR inhibitors, which have the same molecular scaffold, but different physiochemical properties. Rapalogs are being tested in a wide spectrum of human tumors as both monotherapy and a component of combination therapy. Among them, tems...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2015-10, Vol.36 (10), p.1163-1169
Main Authors: Meng, Ling-hua, Zheng, X F Steven
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacology
Antibiotics, Antineoplastic - therapeutic use
Computational Biology - methods
Humans
Molecular Targeted Therapy - methods
Neoplasms - drug therapy
Neoplasms - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Precision Medicine - methods
Review
Signal Transduction - drug effects
Sirolimus - analogs & derivatives
Sirolimus - pharmacology
Sirolimus - therapeutic use
TOR Serine-Threonine Kinases - metabolism
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Summary:Rapamycin and its analogs (rapalogs) are the first generation of mTOR inhibitors, which have the same molecular scaffold, but different physiochemical properties. Rapalogs are being tested in a wide spectrum of human tumors as both monotherapy and a component of combination therapy. Among them, temsirolimus and everolimus have been approved for the treatment of breast and renal cancer. However, objective response rates with rapalogs in clinical trials are modest and variable. Identification of biomarkers predicting response to rapalogs, and discovery of drug combinations with improved efficacy and tolerated toxicity are critical to moving this class of targeted therapeutics forward. This review focuses on the aberrations in the PI3K/mTOR pathway in human tumor cells or tissues as predictive biomarkers for rapalog efficacy. Recent results of combinational therapy using rapalogs and other anticancer drugs are documented. With the rapid development of next-generation genomic sequencing and precision medicine, rapalogs will provide greater benefits to cancer patients.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2015.68