Autophagy and endocrine resistance in breast cancer

Katherine L. Cook, Ayesha N. Shajahan, Robert Clarke

Research output: Contribution to journalReview article

88 Scopus citations

Abstract

The American Cancer Society estimates that over 200,000 new breast cancer cases are diagnosed annually in the USA alone. Of these cases, the majority are invasive breast cancers and almost 70% are estrogen receptor-α positive. Therapies targeting the estrogen receptor-α are widely applied and include selective estrogen receptor modulators such as tamoxifen, a selective estrogen receptor downregulator such as Fulvestrant (Faslodex; FAS, ICI 182,780), or one of the third-generation aromatase inhibitors including letrozole or anastrozole. While these treatments reduce breast cancer mortality, many estrogen receptor-α-positive tumors eventually recur, highlighting the clinical significance of endocrine therapy resistance. The signaling leading to endocrine therapy resistance is poorly understood; however, preclinical studies have established an important role for autophagy in the acquired resistance phenotype. Autophagy is a cellular degradation process initiated in response to stress or nutrient deprivation, which attempts to restore metabolic homeostasis through the catabolic lysis of aggregated proteins, unfolded/misfolded proteins or damaged subcellular organelles. The duality of autophagy, which can be either pro-survival or pro-death, is well known. However, in the context of endocrine therapy resistance in breast cancer, the inhibition of autophagy can potentiate resensitization of previously antiestrogen resistant breast cancer cells. In this article, we discuss the complex and occasionally contradictory roles of autophagy in cancer and in resistance to endocrine therapies in breast cancer.

Original languageEnglish (US)
Pages (from-to)1283-1294
Number of pages12
JournalExpert Review of Anticancer Therapy
Volume11
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • 3-methyladenine
  • antiestrogen resistance
  • aromatase inhibitor
  • autophagy
  • bafilomycin A1
  • breast cancer
  • endoplasmic reticulum stress
  • fulvestrant
  • hydroxychloroquine
  • tamoxifen
  • unfolded protein response

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