Aug 11 : Researchers at Lombardi Comprehensive Cancer Center have found a new gene mechanism that increase resistance to endocrine or anti-hormonal therapies, such as Tamoxifen in breast cancer patients.

The study may help to screen women for responsiveness to these treatments, and provide clue to reversing the resistance.

Anti-hormonal therapies are some of the most effective treatments for breast cancer because estrogen, a natural female sex hormone, can drive the growth of the tumour.

Tamoxifen and other anti-hormonal therapies cut off the tumour’s access to estrogen, causing the tumour to stabilize and sometimes even shrink.

Earlier studied have shown that human X-box binding protein-1 (XBP1), an alternatively spliced transcription factor that participates in a stress-signalling pathway to protect cells from damage is co-expressed with the estrogen receptor in breast tumour cells.

Its over-expression thus meant that these two proteins interact in the cell. And suggested that the XBP1 protein may play a role in breast cancer pathways.

As part of the study Robert Clarke and colleagues examined the changes accompanied with a cell gradually becoming sensitive to endocrine therapy.

The study found that over-expression of the spliced variant of the gene in estrogen receptor-positive breast cancer cells led to reduced sensitivity to Tamoxifen and Faslodex.

“When cell lines changed from being sensitive to endocrine therapy to being resistant, we saw an increase in spliced XBP1 inside the cell. So then we took sensitive cells and added spliced XBP1, which made them resistant to the therapy,” Clarke said.

“XBP1 may give us a much-needed clue for better predicting response to anti-estrogen therapies like Tamoxifen. The presence of the activated protein at high levels should predict estrogen independence and thus resistance to these therapies,” he added.

The findings of the study were published online in the Journal of the Federation of American Societies for Experimental Biology (FASEBJ). (ANI)