Markers of resistance - overcoming resistance to anti-HER2 therapy

[agness]

A collection of recent articles discussing how patients develop resistance to anti-HER2 therapies and some strategies to overcome this resistance.

"Biomarkers with the potential to predict decreased sensitivity, early resistance, or relapse to HER2-directed therapies may include overexpression of truncated HER2 protein (p95HER2); loss of the phosphatase and tensin homolog tumour-suppressor gene or activating mutations in the catalytic or regulatory subunits of phosphatidylinositol-3 kinase (PI3K), which is associated with upregulation of the PI3K/AKT/mTOR pathway; and overexpression of type 1 insulin-like growth factor receptor (Esteva et al, 2010). In patients with HER2-positive MBC, high levels of p95HER2 were found to correlate with decreased progression-free survival (PFS) and OS (Sperinde et al, 2010) and in patients with HER2-positive early-stage breast cancer, increased PI3K pathway activity was associated with a significantly worse OS (Jensen et al, 2012)."

http://www.nature.com/bjc/journal/va...c2014174a.html

Targeting the autophagy pathway to potentiate the efficacy of HER2-targeted drugs in breast cancer. : The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer : Scientific Reports : Nature Publishing Group
http://www.nature.com/srep/2013/1308...p02469_F6.html

PLOS ONE: Autophagy Facilitates the Development of Breast Cancer Resistance to the Anti-HER2 Monoclonal Antibody Trastuzumab
http://www.plosone.org/article/info%...l.pone.0006251

Study Suggests Using Excess Stress to Kill Therapy Resistant Breast Cancer -- CINCINNATI, May 26, 2015 /PRNewswire
http://www.prnewswire.com/news-relea...300088498.html

New approach to treat drug-resistant HER2--positive breast cancer -- ScienceDaily
http://www.sciencedaily.com/releases...0409133220.htm

Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. - PubMed - NCBI
http://www.ncbi.nlm.nih.gov/m/pubmed/22471661/

Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials | BMC Medicine |
http://bmcmedicine.biomedcentral.com...916-014-0132-3

[scrunchthecat]

Thanks, Agness! Hope you are enjoying your holidays.