A drug already used in heart disease could improve the effectiveness of therapies for melanoma

A multi-center study developed by the Biomedical Research Center of navarrabiomed (Pamplona, ​​​​​​Navarra), the CSIC-UMH Institute of Neuroscience (Sant Joan d’Alacant, Valencian Community) and the IRB Barcelona (Barcelona, ​​​​​​Catalonia) show that the application of ranolazinea drug currently in use heart conditionsimprovement in mice the effectiveness of current therapies for the treatment of melanoma.

magazine natural metabolism has published the results of the study that offers a therapeutic alternative for the treatment of melanoma, the type of deadliest skin cancer In Spain, 16.3 women and 14.6 men per 100,000 inhabitants are affected.

The use of the drug ranolazine, which is approved for human use and already used in clinical practice for treatment chronic angina pectoriswould favor the development of future clinical trials to validate and confirm its effects in cancer patients.

Avoid resistance

Most melanoma patients respond well to therapies targeting one of the key genes involved in tumor progression: the BRAF gene. However, they soon develop resistance to these therapies and the tumors grow back. In addition, recent clinical studies suggest that these patients react worse to it immunotherapy.

Using this drug makes melanoma cells more visible to the immune system, which improves the response to immunotherapies

Thanks to this research, a deep understanding of the role of the fatty acid metabolism in the development of resistance to BRAF inhibitors and the effect of ranolazine has been demonstrated slow progression of the tumor.

Importantly, the use of this drug allows melanoma cells to form more visible for the immune system, improves the response to immunotherapies and increases the ability of lymphocytes to control tumor growth.

Multicenter study

The research was coordinated by Navarrabiomed Imanol Arozarena Martinicorenaresponsible for the Cancer Signaling Unit, and is part of the PhD thesis of the Public University of Navarra in Martha Redondo Munoz. It was developed in collaboration with the Institute of Neuroscience (a joint CSIC center and the University of Miguel Hernández), together with researchers from the Cellular Plasticity in Development and Disease group, and with the IRB Barcelona.

“This study shows that it is possible to pharmacologically reorganize the metabolism of the tumor cell in order to improve the effect of targeted therapies and immunotherapies.”

Imanol Arozarena, Principal Investigator

The research and experiments related to resistance to targeted therapies and the study of the effects of ranolazine were designed from Navarrabiomed immunogenicity of melanoma cells.

“This study shows that it is possible pharmacologically reorganize He metabolism of the tumor cell in order to improve the effect of targeted therapies and immunotherapies. The next challenge is to demonstrate the clinical effect of these combinations in patients and to investigate ranolazine’s potential in other cancers. To do this, we need to better understand how this drug works both in tumor cells and in the immune system,” says Arozarena.

Immunotherapy tests with mice were developed at the Institute for Neuroscience Study of immune cells the tumor microenvironment.

“Immunotherapy has established itself as a basic therapy strategy for melanoma and other types of cancer. However, many patients do not respond optimally to these treatments. “This work demonstrates the beneficial effect of combining ranolazine with immunotherapy in preclinical models of melanoma, supporting its potential application in patients,” stressed Berta Sanchez-Laorden.

Meanwhile, at IRB Barcelona, ​​the RNA sequencing analysis of single cells, which allowed us to know in detail the effect of ranolazine on the metabolic state of tumor cells.

Although melanoma accounts for only 10% of skin cancer cases, it accounts for 90% of skin cancer-related deaths

“We suspected that fatty acid metabolism was critical in the most aggressive forms of melanoma, but being able to confirm this with a drug that is already approved for human use is extremely relevant,” he says. Aznar Benitah, who hopes that “these results could be the way to transform clinical practice.”


In the year 2022were diagnosed in Spain 7,500 new cases of cutaneous melanoma. Globally, this type of cancer accounts for 3.4% of all detected cancers. Although melanoma accounts for only 10% of skin cancer cases, it accounts for 90% of skin cancer-related deaths.

Thanks to the advent of targeted therapies and immunotherapies, clinical management of people with melanoma has improved, but 50% of patients still do not respond to these therapies and/or do not develop resistance. The combination of Current therapies with ranolazine could offer a therapeutic alternative for these patients and improve their clinical response.

This study was possible thanks to the institutional support and funding provided by the Ministry of Science and Innovation, the Carlos III Health Institute, the Government of Navarre, the Spanish Multidisciplinary Melanoma Group (GEM) and the Melanoma Research Alliance, among others.


Redondo-Munoz M. et al. “Ranolazine-induced metabolic rewiring improves melanoma response to targeted therapy and immunotherapy.” natural metabolism (2023)

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