New developments in mammalian target of rapamycin inhibitors for the treatment of sarcoma

Mark Agulnik*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Although sarcomas account for a small portion of solid malignancies, currently, there are few treatment options for sarcomas, particularly for advanced disease. The mammalian target of rapamycin (mTOR), a serine-threonine protein kinase in the phosphatidylinositol 3-kinase/serine/threonine protein kinase Akt signaling pathway, has an important role in the regulation of protein synthesis, cell proliferation, angiogenesis, and metabolism. Alterations of the mTOR signaling pathway are common in malignancies, including several types of sarcoma. Therefore, mTOR is a potentially important therapeutic target in these diseases. Rapamycin and its analogs (rapalogs) are effective anticancer agents in a broad range of preclinical models. Clinical trials with these agents alone and in combination with other anticancer agents, including chemotherapy and targeted therapies, have demonstrated potential clinical benefit in several types of sarcoma. The evidence from both preclinical and clinical studies supports further study of mTOR-targeting rapalogs in the treatment of various subtypes of sarcoma.

Original languageEnglish (US)
Pages (from-to)1486-1497
Number of pages12
Issue number6
StatePublished - Mar 15 2012


  • everolimus
  • mammalian target of rapamycin (mTOR) protein
  • ridaforolimus
  • sarcoma
  • sirolimus
  • temsirolimus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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