Type

Other / n/a

Authors

Bryan T Hennessy
Alex J Eustace
John Crown
Sinead Toomey
Denis M Collins
N Elster

Subjects

Microbiology

Topics
humanized phosphatidylinositol 3 kinases humans drug resistance antibodies neoplasm drug resistance neoplasm receptor female medical molecular biology breast neoplasms receptor erbb 2 erbb 2 signal transduction antibodies monoclonal humanized monoclonal medical sciences antineoplastic agents

HER2-family signalling mechanisms, clinical implications and targeting in breast cancer. (2015)

Abstract Approximately 20 % of human breast cancers (BC) overexpress HER2 protein, and HER2-positivity is associated with a worse prognosis. Although HER2-targeted therapies have significantly improved outcomes for HER2-positive BC patients, resistance to trastuzumab-based therapy remains a clinical problem. In order to better understand resistance to HER2-targeted therapies in HER2-positive BC, it is necessary to examine HER family signalling as a whole. An extensive literature search was carried out to critically assess the current knowledge of HER family signalling in HER2-positive BC and response to HER2-targeted therapy. Known mechanisms of trastuzumab resistance include reduced receptor-antibody binding (MUC4, p95HER2), increased signalling through alternative HER family receptor tyrosine kinases (RTK), altered intracellular signalling involving loss of PTEN, reduced p27kip1, or increased PI3K/AKT activity and altered signalling via non-HER family RTKs such as IGF1R. Emerging strategies to circumvent resistance to HER2-targeted therapies in HER2-positive BC include co-targeting HER2/PI3K, pan-HER family inhibition, and novel therapies such as T-DM1. There is evidence that immunity plays a key role in the efficacy of HER-targeted therapy, and efforts are being made to exploit the immune system in order to improve the efficacy of current anti-HER therapies. With our rapidly expanding understanding of HER2 signalling mechanisms along with the repertoire of HER family and other targeted therapies, it is likely that the near future holds further dramatic improvements to the prognosis of women with HER2-positive BC.
Collections Ireland -> Royal College of Surgeons in Ireland -> Molecular Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular Medicine

Full list of authors on original publication

Bryan T Hennessy, Alex J Eustace, John Crown, Sinead Toomey, Denis M Collins, N Elster

Experts in our system

1
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33
 
2
Alex J Eustace
Dublin City University
 
3
John Crown
Dublin City University
Total Publications: 104
 
4
Sinead Toomey
Royal College of Surgeons in Ireland
Total Publications: 26
 
5
Denis M Collins
Dublin City University
Total Publications: 26