Researchers at St, Louis University have  found a molecular signature that may define a particular subset of triple-negative breast cancer,  which can ultimate lead to target therapy for that group of patients.  In specific, they have uncovered a pathway responsible for the loss of 53BP1 in TNBC tumors related to the  BRCA1 mutation. Loss of BRCA1, they discovered,  increases the expression of the protease cathepsin L (CTSL), which causes the degradation of 53BP1. Cells that have lost both BRCA1 and 53BP1 have the ability to repair DNA and proliferate. That means the protease helps cancer cells with faulty BRCA1 survive—it is a defined bad guy in TNBC growth.  And, when we know who the bad guy is, we can stop looking at ways to stop him in his mean old tracks.

The research was published in the Journal of Cell Biology January 17, 2013.
Treatment of BRCA1-deficient tumor cells with vitamin D restores high levels of 53BP1 slows the growth of cancer cells, they discovered.  In addition, vitamin D treatment might restore the sensitivity to PARP inhibitors in patients who become resistant. Thus, a combination of vitamin D and PARP inhibitors could be effective treatment for some TNBC patients.
They also found that some TNBC tumors have:
• high levels of nuclear CTSL
• low levels of 53BP1 and nuclear vitamin D receptor (VDR)

These unique biomarkers can be used for personalized treatment, identifying those who might benefit the most from vitamin D.

Clinical trials are underway to develop  vitamin D and cathepsin inhibitors as single agents or in combination with different drugs.

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Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

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