A drug that is already used for angina pectoris, new promise against melanoma

Ranolazine, a drug commonly used to treat patients with stable angina pectoris, could also be useful against melanoma. This is indicated by a new study carried out by Spanish researchers from the Navarrabiomed Biomedical Research Center, the IRB of Barcelona and the Institute of Neurosciences CSIC-UMH of Alicante.

According to its data, obtained in studies in animal models, the drug improves the efficacy of therapies currently used in the treatment of melanoma, the most aggressive type of skin cancer.. Details of their work are published in the latest issue of the journal Nature Metabolism..

“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..

The researchers, at first, verified that the resistance of the tumor corresponds to a change in its metabolism of fats. They saw that, when it is 'encircled', cancer begins to use fat burning as a survival mechanism, in order to continue growing.

So, they wondered if using a drug that blocks the use of fatty acids by cells could be useful to stop this escape route from cancer.. And they reviewed the options already available on the market for that 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”, points out Imanol Arozarena, head of the Navarrabiomed Cancer Signaling Unit and coordinator of the study..

It worked. In animal studies, the action of ranolazine was capable of slowing down tumor progression and, more importantly, it made the cancer susceptible to the action of immunotherapy.

“The treatment manages, explaining it in a simple way, to make the tumor cells more visible to the immune system”, exemplifies Arozarena.

In the investigation, 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..

In the conclusions of the study, the scientists point out that their data show that ranolazine could be useful for making resistant tumors sensitive to immunotherapy, although they recall that human trials must be carried out to confirm this relationship..

In addition to initiating this pathway, the scientists also want to explore the usefulness of the drug in other types of cancers that also use fat metabolism as a source of energy, as well as advance knowledge of how this drug acts on tumor cells and the immune system.

“Immunotherapy has established itself as a fundamental therapeutic strategy in melanoma and other types of cancer. Despite this, many patients do not respond optimally to these treatments. This work shows the beneficial impact of the combination of ranolazine with immunotherapy in models preclinical studies of melanoma, which supports its possible application in patients”, highlighted Berta Sánchez-Laorden, principal investigator of the Cellular Plasticity in Development and Disease group at the Institute of Neurosciences CSIC-Universidad Miguel Hernández, who has also participated in the investigation.