Clinical activity of mammalian target of rapamycin inhibitors in solid tumors

Yesid Alvarado, Monica M. Mita, Sushma Vemulapalli, Devalingam Mahalingam, Alain C. Mita*

*Corresponding author for this work

Research output: Contribution to journalReview article

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)69-94
Number of pages26
JournalTargeted Oncology
Volume6
Issue number2
DOIs
StatePublished - Jun 1 2011

Keywords

  • Mammalian Target of Rapamycin
  • mTOR
  • mTOR inhibitors
  • Rapalogs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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