Current treatment strategies for inhibiting mTOR in cancer

被引:255
作者
Chiarini, Francesca [1 ,2 ]
Evangelisti, Camilla [1 ,2 ]
McCubrey, James A. [3 ]
Martelli, Alberto M. [4 ]
机构
[1] CNR, Inst Mol Genet, I-40126 Bologna, Italy
[2] Rizzoli Orthoped Inst, Bologna, Italy
[3] E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC USA
[4] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy
关键词
rapamycin; rapalogs; dual PI3K/mTOR inhibitors; ATP-competitive mTOR inhibitors; translation; ADVANCED SOLID TUMORS; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PHASE-I TRIAL; DUAL PI3K/MTOR INHIBITOR; RENAL-CELL CARCINOMA; STEM-LIKE CELLS; MAMMALIAN TARGET; TUBEROUS SCLEROSIS; NEUROENDOCRINE TUMORS;
D O I
10.1016/j.tips.2014.11.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:124 / 135
页数:12
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