Drug Resistance: Conspiracy of Two Protein against Breast Cancer

Breast cancer is the most common malignant tumour among women in the western world, affecting 8-12 % of the female population. In the Netherlands, breast cancer occurs yearly in 1,000 per 100,000 women with an absolute incidence of 9,000 new cases per year.

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Tamoxifen is effective for endocrine treatment of estrogen receptor(ER)-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing estrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, and thereby mediate the cell growth control .

Conspiracy against drug resistance

Scientists at Sanford-Burnham Medical Research Institute provide conclusive evidence that antiestrogen resistance in breast cancer cells requires the interaction between BCAR1 and BCAR3 proteins. This interaction is responsible for resistance to antiestrogen drugs, paving the way for improved diagnostic and treatment strategies.

“Drug resistance is one of the most serious obstacles to breast cancer eradication,” said the senior study author Elena Pasquale, Ph.D., professor. “Our findings suggest that strategies to disrupt the BCAR1-BCAR3 complex and associated signaling networks could potentially overcome this obstacle and ultimately lead to more-effective breast cancer therapies.”

Parkinson’s Drug Shows Promise of prevention

One drug, called benserazide, is currently used for Parkinson’s disease, and in studies it reduced the formation of breast tumors in mice that had been implanted with cancer cells containing the BRCA1 gene mutation. All of the mice that did not receive the drug developed breast tumors, but 40 percent of mice given the drug were tumor-free, said study researcher Elizabeth Alli, of Stanford University School of Medicine.

A prominent role for BRCA1 gene in alternative growth pathways may reflect therapeutic effectiveness of benserazide. As a result describes, high levels of BCAR1/pl30Cas protein in ER-positive primary breast tumours are associated with intrinsic resistance to tamoxifen treatment. Thus, deciphering the expression variance of  BRCA genes is essential for understanding development of resistance of breast cancer.

References:

1. Kuenen-Boumeester V, Hop WCJ, Blonk Dl, Boon ME. Prognostic scoring using cytomorphometry and lymplmode status of patients with breast carcinoma. Ellr J Canw· Cl Oncology, 20(3): 337-345, 1984.

2. Association of the BCAR1 and BCAR3 Scaffolding Proteins in Cell Signaling and Antiestrogen Resistance.  J Biol Chem. 2014 Apr 11;289(15):10431-44.

3. Tamoxifen resistance in breast cancer: elucidating mechanisms. Drugs. 2001;61(12):1721-33.

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