Vitamin D could contribute to breast cancer treatment

Breast cancer: vitamin D could be a valuable supportive therapy
Vitamin D could exert a beneficial role in the treatment of triple-negative breast cancer, one of the most difficult forms of cancer to treat. In fact, the vitamin appears to be able to increase levels of 53BP, a protein necessary for repairing DNA damage and controlling cancer cell proliferation.

This is the complex molecular mechanism discovered by researchers at Saint Louis University in Washington, DC, USA, and described by a paper published in the The Journal of Cell Biology.

The properties of vitamin D
Vitamin D is a fat-soluble vitamin that can be taken in through food, or synthesized in the human body by the action of sunlight. The main function of vitamin D is to maintain normal levels of calcium and phosphorus in the blood and promote calcium absorption, contributing to bone formation and maintaining bone stability. Recently, research has suggested that vitamin D may also have other functions, such as protecting against hypertension and preventing various autoimmune diseases and some cancers.

Triple-negative breast cancer: scovered new molecular mechanism
Triple-negative breast cancer is one of the most treatment-resistant cancers because, lacking receptors for estrogen, progesterone, and epidermal growth factor, it does not respond to some common hormone therapies. Often this type of cancer is caused by a mutation in the BRCA1 gene. This is important because it is involved in DNA damage repair and cell cycle control. Recently, scholars have shown that loss of another DNA repair factor, the 53BP1 protein, allows proliferation and survival of cells with mutation in BRCA1.

Decreased 53BP1 levels have been observed in triple-negative breast cancers, and appear to correlate with resistance to cancer treatment drugs. By studying the complicated interactions involving these molecules, the team of researchers, led by Dr. Gonzalo, discovered the mechanism responsible for the loss of 53BP1 in breast cancers, particularly in BRCA1 mutated and triple-negative breast cancers. Indeed, it appears that in cells with mutation in BRCA1 there is an 'increase in an enzyme, known as cathepsin, which causes the degradation of 53BP1. Thus cells that have lost both BRCA1 and 53BP1 are no longer able to repair DNA, maintain genome integrity and control their own replication. The investigators also found that by treating cancer cells with vitamin D, 53BP1 levels were restored, conferring greater genomic stability and reduced proliferation. Analyzing tumor tissue samples with mutations in BRCA1 or triple-negative, the team of scientists, found high concentrations of cathepsin and low levels of 53BP1 and the vitamin D receptor. The latter are thus true markers to be used to identify those who might most benefit from vitamin D and inhibitors that block the action of cathepsin.

New treatments that include vitamin D
Thanks to these findings, women with triple-negative breast cancer may in the future pursue new therapies that also include vitamin D. Of course, the effectiveness of such treatments will need to be confirmed first. Preclinical studies involving vitamin D and cathepsin inhibitors are currently underway, either as single agents or in combination with different drugs.

Source: A. Grotsky, I. Gonzalez-Suarez, A. Novell, M. A. Neumann, S. C. Yaddanapudi, M. Croke, M. Martinez-Alonso, A. B. Redwood, S. Ortega-Martinez, Z. Feng, E. Lerma, T. Ramon y Cajal, J. Zhang, X. Matias-Guiu, A. Dusso, S. Gonzalo. "BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells. The Journal of Cell Biology, 2013; 200 (2): 187