TY - JOUR
T1 - Current treatment strategies for inhibiting mTOR in cancer
AU - Chiarini, Francesca
AU - Evangelisti, Camilla
AU - McCubrey, James A.
AU - Martelli, Alberto M.
PY - 2015
Y1 - 2015
N2 - Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that regulates a wide range of functions, including cell growth, proliferation, survival, autophagy, metabolism, and cytoskeletal organization. mTOR activity is dysregulated in several human disorders, including cancer. The crucial role of mTOR in cancer cell biology has stimulated interest in mTOR inhibitors, placing mTOR on the radar of the pharmaceutical industry. Several mTOR inhibitors have already undergone clinical trials for treating tumors, without great success, although mTOR inhibitors are approved for the treatment of some types of cancer, including advanced renal cell carcinoma. However, the role of mTOR inhibitors in cancer treatment continues to evolve as new compounds are continuously being disclosed. Here we review the three classes of mTOR inhibitors currently available for treating cancer patients. Moreover, we highlight efforts to identify markers of resistance and sensitivity to mTOR inhibition that could prove useful in the emerging field of personalized medicine.
AB - Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that regulates a wide range of functions, including cell growth, proliferation, survival, autophagy, metabolism, and cytoskeletal organization. mTOR activity is dysregulated in several human disorders, including cancer. The crucial role of mTOR in cancer cell biology has stimulated interest in mTOR inhibitors, placing mTOR on the radar of the pharmaceutical industry. Several mTOR inhibitors have already undergone clinical trials for treating tumors, without great success, although mTOR inhibitors are approved for the treatment of some types of cancer, including advanced renal cell carcinoma. However, the role of mTOR inhibitors in cancer treatment continues to evolve as new compounds are continuously being disclosed. Here we review the three classes of mTOR inhibitors currently available for treating cancer patients. Moreover, we highlight efforts to identify markers of resistance and sensitivity to mTOR inhibition that could prove useful in the emerging field of personalized medicine.
KW - ATP-competitive mTOR inhibitors
KW - dual PI3K/mTOR inhibitors
KW - rapalogs
KW - rapamycin
KW - translation
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U2 - 10.1016/j.tips.2014.11.004
DO - 10.1016/j.tips.2014.11.004
M3 - Article
C2 - 25497227
AN - SCOPUS:84922210268
SN - 0165-6147
VL - 36
SP - 124
EP - 135
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 2
ER -