Dasanu Constantin A, Clark Bernard A, Alexandrescu Doru T
Saint Francis Hospital and Medical Center, Hematology and Medical Oncology, Gothic Park, 43 Woodland Street, Hartford, CT 06105, USA.
Expert Opin Investig Drugs. 2009 Feb;18(2):175-87. doi: 10.1517/13543780902721229.
The mammalian target of rapamycin (mTOR) pathway inhibition has emerged as one of the main directions for the development of new targeted agents in renal cell carcinoma (RCC). A prominent member in its class of medications, temsirolimus has already been shown to improve overall survival in advanced kidney cancer, when compared with the previous standard, IFN-alpha.
The aim of this study was to review the most relevant preclinical and clinical data on the mTOR inhibitors, both in clinical use or in current development.
The authors give a comprehensive review of the existing English literature on the role of the mTOR pathway in renal tumorigenesis, as well as a detailed safety and efficacy analysis of older and newer rapamycin analogs.
RESULTS/CONCLUSIONS: Rapamycin derivatives temsirolimus and everolimus have significant clinical activity in patients with advanced-stage RCC. Both parenteral and oral formulations of mTOR inhibitors have shown clinical efficacy and are currently being developed. Combinations of mTOR inhibitors with VEGF/VEGFR-blocking agents are also being studied, in an attempt to further enhance the antineoplastic effect.
