Abstract
Studies over the last two decades have identified that amplified human epidermal growth factor receptor (HER-2; c-erbB-2, neu) and its overexpression have been frequently implicated in the carcinogenesis and prognosis in a variety of solid tumours, especially breast cancer. Lots of painstaking efforts were invested on the HER-2 targeted agents, and significantly improved outcome and prolonged the survival of patients. However, some patients classified as 'HER-2-positive' would be still resistant to the anti-HER-2 therapy. Various mechanisms of drug resistance have been illustrated and the alteration of HER-2 was considered as a crucial mechanism. However, systematic researches in regard to the HER-2 mutations and variants are still inadequate. Notably, the alterations of HER-2 play an important role in drug resistance, but also have a potential association with the cancer risk. In this review, we summarize the possible mutations and focus on HER-2 variants' role in breast cancer tumourigenesis. Additionally, the alteration of HER-2, as a potential mechanism of resistance to trastuzumab, is discussed here. We hope that HER-2 related activating mutations could potentially offer more therapeutic opportunities to a broader range of patients than previously classified as HER-2 overexpressed.
Highlights
The HER-2 mutations and variants– The HER-2 mutations – The HER-2 variants The HER-2 mutations associated with breast cancer riskThe HER-2 mutations associated with breast cancer resistance – The point or small insertion resistance mutations – The resistance variants of HER-2The therapy methods to these HER-2 mutations Conclusion AbstractStudies over the last two decades have identified that amplified human epidermal growth factor receptor (HER-2; c-erbB-2, neu) and its overexpression have been frequently implicated in the carcinogenesis and prognosis in a variety of solid tumours, especially breast cancer
Human epidermal growth factor receptor-2 gene with some kinase domain mutations shows the characteristics of constitutively activate kinase activity and increased oncogenicity compared to the wild-type
The application of trastuzumab, which targeted against HER-2, has significantly improved the outcome and prognosis of HER-2-overexpressing breast cancer
Summary
The HER-2 mutations and variants– The HER-2 mutations – The HER-2 variants The HER-2 mutations associated with breast cancer riskThe HER-2 mutations associated with breast cancer resistance – The point or small insertion resistance mutations – The resistance variants of HER-2The therapy methods to these HER-2 mutations Conclusion AbstractStudies over the last two decades have identified that amplified human epidermal growth factor receptor (HER-2; c-erbB-2, neu) and its overexpression have been frequently implicated in the carcinogenesis and prognosis in a variety of solid tumours, especially breast cancer. Mutations in TK domain Human epidermal growth factor receptor-2 gene amplification or protein overexpression has been identified as a mechanism of HER-2 activation in breast cancer [1]. Human epidermal growth factor receptor-2 gene with some kinase domain mutations shows the characteristics of constitutively activate kinase activity and increased oncogenicity compared to the wild-type
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
