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Analysis of different HER-2 mutations in breast cancer progression and drug resistance

Zijia Sun1, Yaqin Shi1, Yan Shen1

  • 1Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Journal of Cellular and Molecular Medicine
|August 26, 2015
PubMed

Insights

Human Epidermal Growth Factor Receptor 2 (HER-2) alterations drive cancer and resistance to therapy. Understanding HER-2 mutations offers new treatment avenues for breast cancer patients beyond HER-2 overexpression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Amplified human epidermal growth factor receptor 2 (HER-2) and its overexpression are key in solid tumor carcinogenesis, particularly breast cancer.
  • HER-2 targeted therapies have improved patient outcomes, yet resistance remains a significant clinical challenge.
  • Mechanisms of resistance to anti-HER-2 therapy are diverse, with alterations in HER-2 itself being a crucial factor.

Purpose of the Study:

  • To systematically review HER-2 mutations and variants and their role in breast cancer tumorigenesis.
  • To explore the association between HER-2 alterations and resistance to HER-2 targeted therapies, specifically trastuzumab.
  • To highlight the potential of HER-2 activating mutations as therapeutic targets for a wider patient population.

Main Methods:

  • Literature review and synthesis of existing research on HER-2 mutations and variants.
  • Analysis of documented mechanisms of drug resistance in HER-2 positive cancers.
  • Focus on the role of HER-2 alterations in breast cancer development and treatment response.

Main Results:

  • HER-2 alterations are implicated in both cancer development and resistance to HER-2 targeted therapies.
  • Specific HER-2 mutations and variants contribute to tumorigenesis and reduced efficacy of treatments like trastuzumab.
  • Systematic research on HER-2 mutations and variants is currently limited but crucial for understanding resistance.

Conclusions:

  • HER-2 alterations represent a critical mechanism of resistance to anti-HER-2 therapies.
  • Understanding HER-2 mutations and variants is essential for developing novel therapeutic strategies.
  • Targeting HER-2 activating mutations may expand treatment opportunities for patients with HER-2 related cancers.
Keywords:
HER-2HER-2 mutationbreast cancercancer riskresistancevariants

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