Florence, 2 July 2024 – A particular type of breast cancer, the breast cancer triple negative, affects patients who do not express hormone receptors on tumor cells. The disease is therefore independent of the effects of these molecules and also for this reason has limited therapeutic options outside of chemotherapy and a strong tendency to give recurrences and metastases.
A research group from the University of Florence, led by Andrea Morandi, has identified a higher concentration of polyunsaturated fatty acids in the most aggressive cells of this type of tumor. The scientists thought of exploiting the abnormal lipid metabolism of the tumor as a target for new treatments, as well as to identify innovative diagnostic markers. The results were published in the journal Embo Molecular Medicine in an article entitled “FadS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer”. The research received funding from the AIRC Foundation for Cancer Research, the Cr Florence Foundation and of theAnnastaccatolisa Association Odv. These institutions also supported the work of the young researchers Nicla Lorito and Angela Subbiani, the first signatories of the article, with two scholarships.
“A subgroup of these carcinomas with worse prognosis show high levels of the enzymes FADS1 and FADS2, involved in the production of polyunsaturated fatty acids” – explains the research coordinator Andrea Morandi, professor of Biochemistry at the Department of Experimental and Clinical Biomedical Sciences of the University of Florence -. “Tumor cells that contain a higher concentration of polyunsaturated fatty acids are more vulnerable to ferroptosis, a particular form of cell death. The ferroptosis It can be triggered by drugs that have so far demonstrated some efficacy in preclinical models, but which require further development and testing before they can be used in patients.”
The results of the study – which involved researchers from the Breast Unit of the Careggi University Hospital in Florence, supported by the Fondazione Radioterapia Oncologica – have in particular demonstrated that it is possible to influence the sensitivity of tumor cells to ferroptosis and thus promote their death. The desired effect is obtained by interfering with the FADS1 and FADS2 enzymes or by lowering the concentration of polyunsaturated lipids inside the cell. “We hope – Morandi comments again – that the toxicity problems related to drugs capable of inducing ferroptosis are overcome as soon as possible. Only then will it be possible to move on to clinical studies that can evaluate the safety and efficacy of these drugs by exploiting the metabolic vulnerability of the most aggressive tumors”.
