mTOR Inhibition for Cancer Therapy: Past, Present and Future
Mita, Monica, Mita, Alain, Rowinsky, Eric K. (Eds.)
2015, Approx. 400 p. 15 illus. in color.
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Preclinical and clinical data available on the subject have been integrated
A dedicated chapter on toxicity profile of mTOR inhibitors
Future directions for the development of mTOR inhibitors
Over the last 10 years, inhibitors of mTOR have emerged as a major class of anticancer drugs. Two rapamycin analogs are currently approved for the treatment of renal cell carcinoma, and it is estimated that a variety of other tumor types could benefit from mTOR inhibition, with numerous clinical trials (including pivotal registration trials) already underway. Second-generation small-molecule inhibitors of the pathway have also shown promise in terms of their superior tolerability and efficacy and are undergoing extensive clinical evaluation, with an estimated 30+ compounds currently under evaluation. This book describes the challenges involved in developing mTOR inhibitors for cancer treatment, starting with an in-depth examination of their molecular mechanism of action, with emphasis on the class side-effects, efficacy and mechanisms of resistance, as well as on promising novel directions for their development, including novel compounds and rational combinations with other anti-neoplastic drugs.
Forward.- Past.- mTOR inhibitors: a little bit of history.- Present.- The mTOR pathway .- The evolving role of mTOR inhibitors in renal cell carcinoma.- The role of mTOR inhibitors in breast cancer.- The role of mTOR inhibitors in neuroendocrine tumors.- New indications of mTOR inhibitors in rare tumors.- The role of mTOR inhibitors in the treatment of hematological malignancies.- The clinical pharmacology and toxicity profile of rapalogs.- Resistance to mTOR inhibitors.- Rational combinations of mTOR inhibitors as anticancer strategies.- Future.- Predictive biomarkers of response to mTOR inhibitors.- The potential future indication of rapamycin analogs for the treatment of other solid tumors.- mTOR inhibition beyond rapalogs.- mTOR, aging and cancer: the missing link?.- New study design for mTOR inhibitors and other biological agents.- Future directions for the development of mTOR inhibitors.