Importance of PI3-kinase pathway in response/resistance to aromatase inhibitors

Cynthia X. Ma, Robert J. Crowder, Matthew J. Ellis

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Endocrine therapy has been the most effective treatment modality for hormone receptor positive breast cancer. However, its efficacy has been limited by either de novo or acquired resistance. Recent data indicates that activation of the phosphatidylinositol 3-kinase (PI3K) signaling is associated with the poor outcome luminal B subtype of breast cancer and accompanied by the development of endocrine therapy resistance. Importantly, inhibition of PI3K pathway signaling in endocrine resistant breast cancer cell lines reduces cell survival and improves treatment response to endocrine agents. Interestingly, mutations in PIK3CA, the alpha catalytic subunit of the class IA PI3K, which renders cells dependent on PI3K pathway signaling, is the most common genetic abnormality identified in hormone receptor positive breast cancer. The synthetic lethality observed between estrogen deprivation and PI3K pathway inhibition in estrogen receptor positive (ER+) breast cancer cell lines provides further scientific rational to target both estrogen receptor and the PI3K pathway in order to improve the outcome of ER+ breast cancer.

Original languageEnglish
Pages (from-to)750-752
Number of pages3
JournalSteroids
Volume76
Issue number8
DOIs
StatePublished - Jul 1 2011

Keywords

  • Breast cancer
  • Endocrine therapy
  • Phosphatidylinositol 3-kinase (PI3K)

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