Emerging strategies to overcome resistance to endocrine therapy for breast cancer

Mohammed F Ziauddin, Dong Hua, Shou-Ching Tang

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Endocrine therapy of breast cancer is perhaps the oldest form of effective and well-tolerated targeted cancer systemic treatment, in both the adjuvant and metastatic disease settings. The most commonly used endocrine therapy agents are selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor downregulators. De novo or acquired resistance to these agents is a significant clinical problem. Preclinical and clinical investigations to understand this resistance have yielded significant advances in understanding cell signaling and the possible mechanisms of resistance. These mechanisms of resistance are as diverse as the biology of breast cancer and can arise from alterations in any of the cell signaling pathway components. A growing understanding of these mechanisms has provided rationale for development of strategies to overcome the resistance. Many of these mechanisms of resistance involve adaptive upregulation of alternate signaling pathways, such as growth factor signaling, and cross talk between estrogen receptor and growth factor signaling. Clinical trials are focusing on cotargeting these alternate pathways along with estrogen receptor signaling. It is becoming evident that, as with all cancer therapy, strategies to overcome resistance need to be individualized, and it is important to identify biomarkers to guide the use of these strategies. This manuscript systemically reviews the recent preclinical and clinical trials on the novel and pathway-driven agents that have shown significant promise in enhancing the efficacy and overcoming the resistance in the hormonal treatment of breast cancer. Future directions including biomarker selection and the role of next generation sequencing will be discussed.

Original languageEnglish (US)
Pages (from-to)791-807
Number of pages17
JournalCancer and Metastasis Reviews
Volume33
Issue number2-3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Estrogen Receptors
Breast Neoplasms
Intercellular Signaling Peptides and Proteins
Biomarkers
Clinical Trials
Selective Estrogen Receptor Modulators
Aromatase Inhibitors
Neoplasms
Up-Regulation
Therapeutics
Direction compound

Keywords

  • Breast cancer endocrine therapy resistance
  • Breast cancer targeted therapy
  • Estrogen receptor
  • Growth factor signaling
  • Signaling cross talk and pathway-driven breast cancer agents

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Emerging strategies to overcome resistance to endocrine therapy for breast cancer. / Ziauddin, Mohammed F; Hua, Dong; Tang, Shou-Ching.

In: Cancer and Metastasis Reviews, Vol. 33, No. 2-3, 01.01.2014, p. 791-807.

Research output: Contribution to journalReview article

Ziauddin, Mohammed F ; Hua, Dong ; Tang, Shou-Ching. / Emerging strategies to overcome resistance to endocrine therapy for breast cancer. In: Cancer and Metastasis Reviews. 2014 ; Vol. 33, No. 2-3. pp. 791-807.
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