Bookedited by Monica Mita, Alain Mita, Eric K. Rowinsky.
Summary: 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. 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.
Contents:
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.