Regulation of ERBB3/HER3 signaling in cancer

Kalpana Mujoo _, Byung-Kwon Choi, Zhao Huang, Ningyan Zhang and Zhiqiang An

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Oncotarget. 2014; 5:10222-10236. https://doi.org/10.18632/oncotarget.2655

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Kalpana Mujoo1,2, Byung-Kwon Choi1, Zhao Huang1, Ningyan Zhang1 and Zhiqiang An1

1 Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas

2 Current address: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX


Kalpana Mujoo, email:

Zhiqiang An, email:

Keywords: HER3, NEDD4, Biomarkers, Monoclonal antibodies, Molecular therapeutics

Received: July 25, 2014 Accepted: November 02, 2014 Published: November 02, 2014


ERBB3/HER3 is emerging as a molecular target for various cancers. HER3 is overexpressed and activated in a number of cancer types under the conditions of acquired resistance to other HER family therapeutic interventions such as tyrosine kinase inhibitors and antibody therapies. Regulation of the HER3 expression and signaling involves numerous HER3 interacting proteins. These proteins include PI3K, Shc, and E3 ubiquitin ligases NEDD4 and Nrdp1. Furthermore, recent identification of a number of HER3 oncogenic mutations in colon and gastric cancers elucidate the role of HER3 in cancer development. Despite the strong evidence regarding the role of HER3 in cancer, the current understanding of the regulation of HER3 expression and activation requires additional research. Moreover, the lack of biomarkers for HER3-driven cancer poses a big challenge for the clinical development of HER3 targeting antibodies. Therefore, a better understanding of HER3 regulation should improve the strategies to therapeutically target HER3 for cancer therapy.

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