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Mechanisms of mammalian target of rapamycin inhibition in sarcoma: present and future

Amy R MacKenzie1, Margaret von Mehren

  • 1Temple University Hospital, Internal Medicine, 3401 N. Broad St. 8PP, Philadelphia, PA 19140, USA. amy.mackenzie@tuhs.temple.edu

Expert Review of Anticancer Therapy
|November 22, 2007
PubMed

Insights

The mammalian target of rapamycin (mTOR) pathway regulates cell growth. Inhibitors of this pathway, like rapamycin analogues, show promise in treating sarcoma by suppressing cancer cell metabolism and protein synthesis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The mammalian target of rapamycin (mTOR) is a key protein kinase regulating cell growth and development.
  • mTOR is part of the PI3K/Akt pathway, responding to growth factors and nutrient availability.
  • Understanding mTOR's regulators and targets has enabled the development of novel anticancer drugs.

Purpose of the Study:

  • To review the role of mTOR inhibitors in sarcoma treatment.
  • To highlight current clinical trials involving rapamycin and its analogues for sarcoma.

Main Methods:

  • Review of scientific literature on mTOR pathway and sarcoma.
  • Analysis of data from clinical trials of mTOR inhibitors.

Main Results:

  • Rapamycin and three analogues (temsirolimus, everolimus, AP23573) are in clinical trials.
  • These inhibitors target protein synthesis and metabolism in cancer cells.

Conclusions:

  • mTOR inhibitors represent a promising therapeutic strategy for sarcoma.
  • Further evaluation in clinical trials is ongoing for these novel anticancer agents.

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