HER3 signaling and targeted therapy in cancer

  • Rosalin Mishra | mishrarn@ucmail.uc.edu James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States. http://orcid.org/0000-0002-9808-8797
  • Hima Patel James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States.
  • Samar Alanazi James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States.
  • Long Yuan James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States.
  • Joan T. Garrett James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States.


ERBB family members including epidermal growth factor receptor (EGFR) also known as HER1, ERBB2/HER2/Neu, ERBB3/HER3 and ERBB4/HER4 are aberrantly activated in multiple cancers and hence serve as drug targets and biomarkers in modern precision therapy. The therapeutic potential of HER3 has long been underappreciated, due to impaired kinase activity and relatively low expression in tumors. However, HER3 has received attention in recent years as it is a crucial heterodimeric partner for other EGFR family members and has the potential to regulate EGFR/HER2-mediated resistance. Upregulation of HER3 is associated with several malignancies where it fosters tumor progression via interaction with different receptor tyrosine kinases (RTKs). Studies also implicate HER3 contributing significantly to treatment failure, mostly through the activation of PI3K/AKT, MAPK/ERK and JAK/STAT pathways. Moreover, activating mutations in HER3 have highlighted the role of HER3 as a direct therapeutic target. Therapeutic targeting of HER3 includes abrogating its dimerization partners’ kinase activity using small molecule inhibitors (lapatinib, erlotinib, gefitinib, afatinib, neratinib) or direct targeting of its extracellular domain. In this review, we focus on HER3-mediated signaling, its role in drug resistance and discuss the latest advances to overcome resistance by targeting HER3 using mono- and bispecific antibodies and small molecule inhibitors.


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HER3, monoclonal antibodies, targeted therapy.
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PlumX Metrics provide insights into the ways people interact with individual pieces of research output (articles, conference proceedings, book chapters, and many more) in the online environment. Examples include, when research is mentioned in the news or is tweeted about. Collectively known as PlumX Metrics, these metrics are divided into five categories to help make sense of the huge amounts of data involved and to enable analysis by comparing like with like.

How to Cite
Mishra, R., Patel, H., Alanazi, S., Yuan, L., & Garrett, J. T. (2018). HER3 signaling and targeted therapy in cancer. Oncology Reviews, 12(1). https://doi.org/10.4081/oncol.2018.355