Inhibitors of mammalian target of rapamycin as novel antitumor agents: From bench to clinic

Shile Huang, Peter J. Houghton

Research output: Contribution to journalReview articlepeer-review

187 Scopus citations

Abstract

Rapamycin and its derivatives, CCI-779 and RAD-001, inhibit the mammalian target of rapamycin (mTOR), downregulating translation of specific mRNAs required for cell cycle progression from G1 to S phase. Preclinically, mTOR inhibitors potently suppress growth and proliferation of numerous tumor cell lines in culture or when grown in mice as xenografts. CCI-779 and RAD-001 are being developed as antitumor drugs and are undergoing clinical trials. Clinically, CCI-779 has shown evidence of antitumor activity but induced relatively mild side effects in patients. Here we discuss potential antitumor mechanisms and resistance mechanisms of mTOR inhibitors, and summarize the current status of these compounds as novel antitumor agents.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalCurrent Opinion in Investigational Drugs
Volume3
Issue number2
StatePublished - 2002
Externally publishedYes

Keywords

  • Antitumor
  • Cell cycle
  • Mammalian target of rapamycin (mTOR)
  • Rapamycin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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