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Insulin-like growth factors, insulin, and growth hormone signaling in breast cancer: implications for targeted

Heather Beckwith1, Douglas Yee2

  • 1Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
|October 10, 2014
PubMed
Abstract

Insights

Targeting growth factor pathways like insulin-like growth factor (IGF), insulin, and growth hormone (GH) shows promise in overcoming breast cancer treatment resistance. However, targeting these receptors alone has not improved patient survival due to pathway redundancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen and HER2 receptors are key targets in breast cancer therapy.
  • Growth factors, including IGF, insulin, and GH, are linked to breast cancer development and progression.
  • These growth factors are implicated in resistance to anti-estrogen and HER2-targeted therapies.

Purpose of the Study:

  • To review growth factor pathways involved in breast cancer treatment resistance.
  • To examine the role of IGF, insulin, and GH signaling in breast cancer.
  • To understand the reasons for the lack of clinical success in targeting these pathways.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of growth factor receptor signaling pathways in breast cancer.
  • Examination of downstream kinases activated by IGF, insulin, and GH receptors.

Main Results:

  • Preclinical studies show that blocking IGF, insulin, and GH receptors inhibits breast cancer growth and resistance.
  • Clinical trials targeting these receptors have not significantly improved patient survival.
  • Pathway redundancy, where IGF, insulin, and GH receptors activate common PI3K and MAPK pathways, explains the lack of clinical benefit.

Conclusions:

  • Multitargeted blockade of growth factor receptors is necessary for effective breast cancer treatment.
  • Simultaneous targeting of downstream kinases like PI3K and MAPK may overcome resistance.
  • Future breast cancer therapies should consider combined blockade strategies.

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