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An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
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Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals

Małgorzata Szostakowska1, Alicja Trębińska-Stryjewska1, Ewa Anna Grzybowska1

  • 1Department of Molecular and Translational Oncology, The Maria Skłodowska-Curie Institute of Oncology, Roentgena 5, Warsaw, Poland.

Breast Cancer Research and Treatment
|November 2, 2018
PubMed
Abstract

Insights

Resistance to anti-estrogen therapy in estrogen receptor-positive breast cancer (ERα+) is a major challenge. This review details molecular changes driving endocrine resistance, enabling tumor growth independent of estrogen.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen receptor alpha (ERα+) drives the majority of breast cancers (BCs).
  • Anti-estrogen therapies targeting ERα are standard for ERα+ BC treatment.
  • A significant percentage of patients develop acquired resistance to endocrine therapy, leading to relapse.

Purpose of the Study:

  • To comprehensively review the molecular mechanisms underlying resistance to anti-estrogen therapy in ERα+ breast cancer.
  • To elucidate how molecular alterations lead to estrogen-independent tumor growth.

Main Methods:

  • Literature review of studies on endocrine resistance in breast cancer.
  • Analysis of genetic, regulatory, and protein-level modifications of ERα.
  • Investigation of alternative growth pathways and cell survival mechanisms.

Main Results:

  • Acquired resistance stems from molecular changes allowing tumor growth irrespective of estrogen.
  • Alterations can involve ERα genetic, regulatory, or protein modifications.
  • Activation of alternate growth pathways and survival mechanisms contribute to estrogen-independence.

Conclusions:

  • Understanding these resistance mechanisms is crucial for improving ERα+ BC treatment outcomes.
  • Focus on genetic alterations, stress responses, cell survival, and reprogramming offers therapeutic targets.
  • Developing strategies to overcome endocrine resistance is essential for long-term patient survival.
Keywords:
Breast cancerEndocrine therapyMolecular mechanismsResistance

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