Spanish scientists find the mechanism that promotes breast cancer metastasis

More than 34,000 women in Spain and two million worldwide are diagnosed with breast cancer each year. Survival rates for the disease are high, reaching 90% when the tumor is located in the breast. But in one in eight patients, cancer cells will spread outside the breast tissue and cause metastases to other organs, worsening the prognosis.

In the fight against the disease, scientists at the Barcelona Biomedical Research Institute (IRB) had for some time focused their research on the MAF protein, which activates or blocks many other genes in tumors. and favors metastasis, especially in dissemination to the bone. But now they have taken a step further by discovering that this protein interacts with the estrogen receptor, a key element in the development of cancer, and modifies its structure. It is this contact between MAF and the estrogen receptor that causes a DNA restructuring that allows the activation of metastasis genes.

The conclusion, published in the scientific journal Nature Cell Biology, is that patients with high levels of MAF protein have a higher risk of developing metastasis. The finding has an important practical application. Researchers believe that the activation of prometastatic genes can be prevented by inhibiting the KDM1A molecule, responsible for DNA restructuring.

At this point, the path is advanced. The KDM1A protein already has an identified inhibitor that is in the clinical trial phase, pending its efficacy and safety being validated, which would offer great benefits to patients with high levels of MAF.

The research, which has received support from the laCaixa Foundation, will also make it possible to advance research into the effects of therapy with bisphosphonates (clodronate or zoledronic acid), which is used in a portion of those diagnosed, but particularly in patients young, can divert metastasis to other organs, which has a negative impact on overall survival.

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“This discovery represents a critical step in understanding how breast cancer spreads and opens new therapeutic opportunities for the 20% of patients who cannot benefit from bisphosphonate treatment,” says Roger Gomis, head of the Breast Cancer Control Laboratory. Cancer Growth and Metastasis from IRB Barcelona.

In this line of work, the IRB team, a leader at the national and international levels, has also developed a test that allows predicting the prognosis of patients with breast cancer. Named MAF-TEST and marketed by Palex Medical and Inbiomotion, the technique is based on the identification of the MAF protein.

By analyzing biopsies of patients from two reference clinical trials (published in The Lancet Oncology and Journal of National Cancer Institute, with more than 3,000 participants in each of them), they discovered that 80% of patients with breast cancer had tumors MAF negative and that when treated with bisphosphonates their disease-free survival increased by 14.3% and their relative risk of death decreased by 21.4%. In contrast, patients with MAF-positive tumors did not obtain any benefit, or even a worse prognosis, with treatment with bisphosphonates. For this second group, yesterday’s progress is even more important.

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