RET in breast cancer: functional and therapeutic implications

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 co...

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Bibliographic Details
Published in:Trends in molecular medicine 2011-03, Vol.17 (3), p.149-157
Main Authors: Morandi, Andrea, Plaza-Menacho, Ivan, Isacke, Clare M
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Breast Neoplasms - genetics
Female
Humans
Pathology
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins c-ret - antagonists & inhibitors
Proto-Oncogene Proteins c-ret - genetics
Proto-Oncogene Proteins c-ret - metabolism
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Summary: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.
ISSN:1471-4914
1471-499X
1471-499X
DOI:10.1016/j.molmed.2010.12.007