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Updated: Apr 7, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
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HOXB7 Is an ERα Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance

Kideok Jin1, Sunju Park1, Wei Wen Teo1

  • 1Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Cancer Discovery
|July 17, 2015
PubMed
Abstract

Insights

The study reveals that the MYC-HOXB7-HER2 pathway drives tamoxifen resistance in breast cancer. Targeting MYC reverses this resistance and shrinks tumors, offering a new therapeutic strategy for endocrine-resistant breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tamoxifen resistance in estrogen receptor-α (ERα)-positive breast cancer remains a clinical challenge.
  • The mechanisms underlying resistance and high HER2 expression are not fully understood.

Purpose of the Study:

  • To elucidate the role of HOXB7 in tamoxifen resistance and HER2 overexpression.
  • To identify regulatory factors controlling HOXB7 expression.
  • To explore therapeutic strategies targeting this pathway.

Main Methods:

  • Chromatin immunoprecipitation assays to assess HOXB7-ERα interaction.
  • Analysis of gene transcription and protein expression.
  • In vitro and in vivo studies using small-molecule inhibitors of MYC.

Main Results:

  • HOXB7 acts as a cofactor for ERα, enhancing transcription of ER target genes, including HER2.
  • MYC stabilizes itself through EGFR-HER2 signaling, inhibiting miR-196a (a HOXB7 repressor).
  • Increased HOXB7 leads to elevated ER target genes and HER2 expression, driving tamoxifen resistance.
  • Repressing MYC reversed resistance and caused breast cancer xenograft regression.

Conclusions:

  • HOXB7 is a key ERα cofactor in tamoxifen-resistant breast cancer, regulating HER2 expression.
  • The MYC-miR-196a axis controls HOXB7 levels.
  • MYC antagonists effectively reverse endocrine resistance in vitro and in vivo.

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