Melanoma is the most aggressive type of skin cancer and, despite the fact that its prevention is possible with adequate protection against solar radiation, only in 2020 around 325,000 new cases of melanoma were diagnosed and some 57,000 people died from it. causes worldwide, according to data from the International Agency for Research on Cancer, whose experts predict that the number of new cases of this skin cancer will increase by more than 50% by 2040 (to more than 500,000 per year), and the number of deaths from the disease will increase by more than two-thirds, to nearly 100,000 per year.
Spanish scientists have now verified that a drug that is already used to treat patients with stable angina pectoris called ranolazine could improve the therapies used to combat melanoma, according to the results of an investigation that they have carried out in animal models and has been published in the scientific journal Nature Metabolism.
The new study has been carried out by researchers from the Navarrabiomed Biomedical Research Center, the IRB of Barcelona and the Institute of Neurosciences CSIC-UMH of Alicante, who have verified that this drug improves the efficacy of therapies used in the treatment of melanoma in the present.
“One of the problems we currently face with melanoma is that it develops resistance to treatments,” explains Salvador Aznar-Benitah, ICREA researcher, head of the Stem Cells and Cancer and Systemic Metabolic Alterations in Cancer laboratories at the IRB. of Barcelona and one of the main signatories of the research.
“Most patients initially respond well to therapies directed against BRAF”, a key mutation for tumor progression that is present in approximately 50% of those affected. But after a few months, “the tumor develops resistance and they are no longer effective,” says the researcher. These patients also respond worse to another of the tools against cancer that is used in the case of melanoma, immunotherapy.
Ranolazine favors the action of immunotherapy against melanoma
The authors of the work observed that the resistance of the tumor corresponds to a change in its metabolism of fats; specifically, that, when it is ‘encircled’, cancer begins to use fat burning as a survival mechanism in order to continue growing. For this reason, they considered whether using a drug that blocked the use of fatty acids by cells could stop this escape route from cancer, and they reviewed the pharmacological options already approved and that served their purpose.
“Although it is not its key function, ranolazine’s ability to block the use of fatty acids by cells has been described. It is a drug already approved for use in patients, so we decided to study it”, says Imanol Arozarena, head of the Navarrabiomed Cancer Signaling Unit and coordinator of the study.
The strategy worked and they found that ranolazine was able to slow tumor progression in animal studies and, more importantly, made the cancer amenable to immunotherapy. “The treatment manages, explaining it in a simple way, to make the tumor cells more visible to the immune system,” explains Arozarena.
The researchers verified that the combination of ranolazine together with a type of immunotherapy (anti-PD-L1 antibodies) achieved very significant improvements both in the response to treatment and in the survival of the treated animals, for which they consider that this drug could prove useful in making resistant tumors sensitive to immunotherapy, although they caution that human trials are still needed to confirm this.
