Targeting the mTOR/4E-BP pathway in endometrial cancer

Clin Cancer Res. 2011 Dec 15;17(24):7518-28. doi: 10.1158/1078-0432.CCR-11-1664. Epub 2011 Dec 5.

Abstract

Endometrial cancer is the most common gynecologic malignancy. Although it is highly treatable in the early stages of disease, therapies for advanced and recurrent disease are rarely curative. A molecular and genetic understanding of endometrial cancer involves the mTOR signaling pathway, an emerging target for treatment of type I disease (the most common presentation). Endometrial cancers show a significant reliance on the mTOR pathway for survival, and studies to date have revealed a clinical advantage in targeting this pathway. Less well developed in the study of endometrial cancer is an understanding of mTOR signaling to its major downstream effector, translational control. Given the poor rate of success for treatment of late-stage endometrial cancer, increasing attention is being directed to the development of new therapeutic approaches, including targeting the mTOR pathway. Here, we discuss the potential benefit of targeting mTOR combined with existing chemotherapies by monitoring its impact on translational regulatory pathways and key translation targets in endometrial cancer. We also highlight laboratory and clinical research findings that will provide new avenues for future research and clinical development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antibiotics, Antineoplastic / therapeutic use
  • Cell Cycle Proteins
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Female
  • Humans
  • Phosphoproteins / metabolism*
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Signal Transduction / drug effects*
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibiotics, Antineoplastic
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus