Clinical activity of mammalian target of rapamycin inhibitors in solid tumors.

Published

Journal Article (Review)

The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway is vital for cell metabolism, growth, and proliferation. mTOR is frequently upregulated in many tumor types and hence has become an important target in cancer treatment. Sirolimus and its derivatives (rapalogs) interact with the intracellular receptor FK506 binding protein 12 (FKBP12), forming a complex with high affinity for mTOR and thus disrupting its activity. Rapalogs are being evaluated extensively in cancer patients with different formulations and schedules. Significant clinical activity has led to their approval for the treatment of kidney cancer, mantle cell lymphoma, and subependymal giant cell astrocytoma; however, despite increasing knowledge about cancer cell biology, their activity in other malignancies is unclear. Further research is needed to identify optimal dosage, administration and targeted combination as well as the subset of patients likely to respond to mTOR/PI3K inhibition. This review focuses on a discussion of the pathway, its implications in cancer biology and results of clinical trials of rapalogs alone or in combination, organizing them by common malignancy type.

Full Text

Duke Authors

Cited Authors

  • Alvarado, Y; Mita, MM; Vemulapalli, S; Mahalingam, D; Mita, AC

Published Date

  • June 2011

Published In

Volume / Issue

  • 6 / 2

Start / End Page

  • 69 - 94

PubMed ID

  • 21541789

Pubmed Central ID

  • 21541789

Electronic International Standard Serial Number (EISSN)

  • 1776-260X

Digital Object Identifier (DOI)

  • 10.1007/s11523-011-0178-5

Language

  • eng

Conference Location

  • France