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HER3 signaling and targeted therapy in cancer

Rosalin Mishra1, Hima Patel1, Samar Alanazi1

  • 1James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA.

Oncology Reviews
|July 31, 2018
PubMed

Insights

HER3 (ErbB3) is crucial in cancer progression and drug resistance, often overlooked due to its low kinase activity. Targeting HER3 offers new therapeutic strategies against various malignancies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • The ErbB receptor family, including EGFR (HER1), HER2, HER3, and HER4, are key targets in precision cancer therapy.
  • HER3 (ErbB3) has gained attention for its role as a heterodimeric partner and in mediating resistance to EGFR/HER2 therapies, despite its impaired kinase activity.

Purpose of the Study:

  • To review HER3-mediated signaling pathways in cancer.
  • To elucidate the role of HER3 in treatment failure and drug resistance.
  • To discuss novel therapeutic strategies targeting HER3.

Main Methods:

  • Literature review of studies on HER3 signaling, resistance mechanisms, and therapeutic targeting.
  • Analysis of HER3's role in activating PI3K/AKT, MAPK/ERK, and JAK/STAT pathways.
  • Examination of therapeutic approaches including small molecule inhibitors and antibodies.

Main Results:

  • HER3 upregulation drives tumor progression through interactions with various receptor tyrosine kinases (RTKs).
  • HER3 activation is implicated in treatment failure, primarily via PI3K/AKT, MAPK/ERK, and JAK/STAT pathways.
  • Activating mutations in HER3 identify it as a direct therapeutic target.

Conclusions:

  • Targeting HER3, either directly or through its dimerization partners, presents a promising strategy to overcome treatment resistance.
  • Novel therapeutic agents, including mono- and bispecific antibodies and small molecule inhibitors, are being developed to effectively target HER3.
Keywords:
HER3monoclonal antibodiestargeted therapy

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