Advances in mechanisms of resistance to aromatase inhibitors

Saranya Chumsri, Amanda Schech, Chakkapong Chakkabat, Gauri Sabnis, Angela Brodie

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Clinically, there are two distinct types of aromatase inhibitor (AI) resistance, namely acquired and innate resistance. Because the underlying mechanisms of these two types of resistance may not be mutually exclusive, strategies to tackle these resistances may not be effective when used interchangeably. Activation of growth factor receptor pathways is the hallmark of acquired AI resistance. These pathways can be targeted either at the cell surface receptor level or their downstream signaling cascades. Currently, everolimus in combination with exemestane represents a new standard of care for patients progressing on non-steroidal AIs. HDAC inhibitors have also shown promising results For innate resistance, the combination of fulvestrant and AI in the front line setting represents a new treatment option, particularly for patients who present with de novo metastatic disease. A Phase III trial is currently ongoing to evaluate the benefit of CDK 4/6 inhibitor, palbociclib, in the first line setting in combination with AI.

Original languageEnglish (US)
Pages (from-to)381-393
Number of pages13
JournalExpert review of anticancer therapy
Volume14
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • CDK4/6 inhibitor
  • HER2
  • aromatase inhibitors
  • breast cancer
  • everolimus
  • fulvestrant
  • growth factor receptor pathways
  • mTOR inhibitors
  • resistance to aromatase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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