REVIEW: The Role of ERBB2/HER2 Tyrosine Kinase Receptor in the Regulation of Cell Death

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A. A. Daks^1#, O. A. Fedorova^1#, O. Y. Shuvalov¹, S. E. Parfenev¹, and N. A. Barlev^1,2,a*

¹Institute of Cytology, Russian Academy of Sciences, 194064 Saint Petersburg, Russia

²Moscow Institute of Physics and Technology (MIPT), 141701 Dolgoprudny, Moscow Region, Russia

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received July 24, 2020; Revised August 10, 2020; Accepted August 12, 2020

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HER2 (Human Epidermal Growth Factor Receptor 2), also known as ERBB2, CD340, and Neu protooncogene, is a member of the epidermal growth factor receptor (EGRF) family. Members of the ERBB family, including HER2, activate molecular cascades that stimulate proliferation and migration of cancer cells, as well as their resistance to the anticancer therapy. These proteins are often overexpressed and/or mutated in various cancer types and represent promising targets for the anti-cancer therapy. Currently, anti-HER2 drugs have been approved for the treatment of several types of solid tumors. HER2-specific therapy includes monoclonal antibodies and low-molecular weight inhibitors of tyrosine kinase receptors, such as lapatinib, neratinib, and pyrotinib. In addition to the activation of molecular pathways responsible for cell proliferation and survival under stress conditions, HER2 directly regulates programmed cell death. Here, we review the studies focused on the involvement of HER2 in various signaling pathways and its role in the regulation of apoptosis.

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KEY WORDS: HER2, epidermal growth factor receptor, cancer, PI3K-AKT signaling pathway, apoptosis

DOI: 10.1134/S0006297920100156

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