Targeting of erbB3 receptor to overcome resistance in cancer treatment

Molecular Cancer

Review

Hui Lyu¹  Jingcao Huang¹  Bolin Liu¹  Jian Ma² 

[1] Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;International Medical Centre of PLA General Hospital, Beijing, China;

关键词: erbB3;    Cell signaling;    Drug resistance;    Targeted therapy;    Cancer;   

DOI  :  10.1186/1476-4598-13-105

 received in 2014-02-26, accepted in 2014-05-02,  发布年份 2014

来源: Springer

【 摘 要 】

The erbB receptors, including the epidermal growth factor receptor (EGFR), erbB2 (also known as HER2/neu), erbB3 (or HER3), and erbB4 (or HER4), are often aberrantly activated in a wide variety of human cancers. They are excellent targets for selective anti-cancer therapies because of their transmembrane location and pro-oncogenic activity. While several therapeutic agents against erbB2 and/or EGFR have been used in the treatment of human cancers with efficacy, there has been relatively less emphasis on erbB3 as a molecular target. Elevated expression of erbB3 is frequently observed in various malignancies, where it promotes tumor progression via interactions with other receptor tyrosine kinases (RTKs) due to its lack of or weak intrinsic kinase activity. Studies on the underlying mechanisms implicate erbB3 as a major cause of treatment failure in cancer therapy, mainly through activation of the PI-3 K/Akt, MEK/MAPK, and Jak/Stat signaling pathways as well as Src kinase. It is believed that inhibition of erbB3 signaling may be required to overcome therapeutic resistance and effectively treat cancers. To date, no erbB3-targeted therapy has been approved for cancer treatment. Targeting of erbB3 receptor with a monoclonal antibody (Ab) is the only strategy currently under preclinical study and clinical evaluation. In this review, we focus on the role of erbB3-initiated signaling in the development of cancer drug resistance and discuss the latest advances in identifying therapeutic strategies inactivating erbB3 to overcome the resistance and enhance efficacy of cancer therapeutics.

【 授权许可】

Unknown   
© Ma et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.