Targeting bone metastatic cancer: Role of the mTOR pathway

Biochim Biophys Acta. 2014 Apr;1845(2):248-54. doi: 10.1016/j.bbcan.2014.01.009. Epub 2014 Feb 5.

Abstract

One of the great challenges of cancer medicine is to develop effective treatments for bone metastatic cancer. Most patients with advanced solid tumors will develop bone metastasis and will suffer from skeletal related events associated with this disease. Although some therapies are available to manage symptoms derived from bone metastases, an effective treatment has not been developed yet. The mammalian target of rapamycin (mTOR) pathway regulates cell growth and survival. Alterations in mTOR signaling have been associated with pathological malignancies, including bone metastatic cancer. Inhibition of mTOR signaling might therefore be a promising alternative for bone metastatic cancer management. This review summarizes the current knowledge on mTOR pathway signaling in bone tissue and provides an overview on the known effects of mTOR inhibition in bone cancer, both in in vitro and in vivo models.

Keywords: Bone metastatic cancer; Cellular signaling; Everolimus; Osteoblast; Osteoclast; mTOR.

Publication types

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

MeSH terms

  • Animals
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Bone and Bones
  • Cell Proliferation / drug effects
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Signal Transduction / genetics*
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus