Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance

Crit Rev Oncol Hematol. 2015 Dec;96(3):507-17. doi: 10.1016/j.critrevonc.2015.07.005. Epub 2015 Jul 18.

Abstract

The phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is one of the most frequently activated signaling pathways in prostate cancer (CaP) and other cancers, and responsible for the survival, metastasis and therapeutic resistance. Recent advances in radiation therapy indicate that activation of this pathway is closely associated with cancer radioresistance, which is a major challenge for the current CaP radiation treatment. Therefore, targeting this pathway by inhibitors to enhance radiosensitivity has great potential for clinical benefits of CaP patients. In this review, we summarize the recent findings in the PI3K/Akt/mTOR pathway in CaP radiotherapy research and discuss the potential use of the PI3K/Akt/mTOR pathway inhibitors as radiosensitizers in the treatment of CaP radioresistance in preclinical studies to explore novel approaches for future clinical trials.

Keywords: Inhibitors; PI3K/Akt/mTOR; Prostate cancer; Radiation therapy; Radioresistance.

Publication types

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

MeSH terms

  • Humans
  • Male
  • Phosphoinositide-3 Kinase Inhibitors*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Radiation Tolerance / drug effects*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Radiation-Sensitizing Agents
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases