Vitamin D May Help Treat Breast Cancer
Breast cancer: vitamin D could be a valuable supportive therapy
Vitamin D may play a beneficial role in the treatment of triple-negative breast cancer, one of the most difficult tumor types to treat. The vitamin appears capable of increasing levels of 53BP, a protein necessary for DNA damage repair and for controlling tumor cell proliferation.
This is the complex molecular mechanism discovered by researchers at Saint Louis University in Washington (USA), described in an article published in The Journal of Cell Biology.
The properties of vitamin D
Vitamin D is a fat-soluble vitamin that can be obtained through diet or synthesized in the human body via sunlight exposure. The main function of vitamin D is to maintain normal calcium and phosphorus levels in the blood and promote calcium absorption, contributing to bone formation and maintaining their stability. Recently, research has suggested that vitamin D may also perform other functions, such as protecting against hypertension, preventing various autoimmune diseases, and some types of cancer.
Triple-negative breast cancer: new molecular mechanism discovered
Triple-negative breast cancer is one of the most resistant cancers to treatment because, lacking receptors for estrogen, progesterone, and epidermal growth factor, it does not respond to some common hormonal therapies. This cancer type is often caused by a mutation in the BRCA1 gene, which is important because it is involved in DNA damage repair and cell cycle control. Recently, researchers have shown that the loss of another DNA repair factor, the protein 53BP1, allows the proliferation and survival of cells with BRCA1 mutation.
Reduced levels of 53BP1 have been observed in triple-negative breast tumors and seem correlated with resistance to cancer treatment drugs. By studying the complex interactions involving these molecules, the research team led by Dr. Gonzalo discovered the mechanism responsible for the loss of 53BP1 in breast tumors, especially those mutated in BRCA1 and triple-negative. It appears that in cells with BRCA1 mutation, there is an increase of an enzyme called cathepsin, which causes degradation of 53BP1. Thus, cells lacking both BRCA1 and 53BP1 can no longer repair DNA, maintain genome integrity, or control their replication. The researchers also found that treating tumor cells with vitamin D restored 53BP1 levels, conferring greater genomic stability and reduced proliferation. Analyzing tumor tissue samples with BRCA1 mutations or triple-negative status, the scientists found high concentrations of cathepsin and low levels of 53BP1 and the vitamin D receptor. These last markers could be used to identify patients who might benefit most from vitamin D and cathepsin inhibitors.
New treatments including vitamin D
Thanks to these discoveries, women with triple-negative breast cancer could in the future undergo new therapies that also include vitamin D. Obviously, it will be necessary to confirm the effectiveness of these treatments first. Currently, preclinical studies involving vitamin D and cathepsin inhibitors are ongoing, both as single agents and in combination with various 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
