RET in breast cancer: functional and therapeutic implications

Trends Mol Med. 2011 Mar;17(3):149-57. doi: 10.1016/j.molmed.2010.12.007. Epub 2011 Jan 19.


Recent studies demonstrate that the receptor tyrosine kinase RET is overexpressed in a subset of ER-positive breast cancers and that crosstalk between RET and ER is important in responses to endocrine therapy. The development of small molecular inhibitors that target RET allows the opportunity to consider combination therapies as a strategy to improve response to treatment and to prevent and combat endocrine resistance. This review discusses: (i) the current knowledge about RET, its co-receptors and ligands in breast cancer; (ii) the breast cancer clinical trials involving agents that target RET; and (iii) the challenges that remain in terms of specificity of available inhibitors and in understanding the complex molecular mechanisms that underlie the resistance to endocrine therapy.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Female
  • Humans
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-ret / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins c-ret / metabolism*


  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-ret