2023-08-10 17:00:06
A multicenter investigation developed by the Biomedical Research Center of Navarrabiomed (Pamplona, Navarra), the CSIC-UMH Institute of Neurosciences (Sant Joan d’Alacant, Valencian Community) and the IRB Barcelona (Barcelona, Catalonia) show that the application of blue watera drug currently used in heart conditionsimprovement in mice the efficacy of current therapies for the treatment of melanoma.
Magazine Nature Metabolism has published the results of the study that offers a therapeutic alternative to treat melanoma, the type of deadliest skin cancer which affects 16.3 women and 14.6 men per 100,000 inhabitants in Spain.
The use of the drug ranolazine, approved for use in humans and which is already being administered in clinical practice to treat chronic anginawould favor the development of future clinical trials to validate and confirm its action in cancer patients.
Avoid resistances
Patients with melanoma in most cases respond well to therapies directed against one of the key genes in tumor progression: the BRAF gene. However, they soon develop resistance to these therapies and the tumors grow back. In addition, the latest clinical studies suggest that these patients respond worse to immunotherapy.
The application of this drug allows melanoma cells to be more visible to the immune system, improving 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 action of ranolazine has been demonstrated to slow tumor progression.
What is still important is that the application of this drug allows melanoma cells to be more visible for the immune system, improving the response to immunotherapies and increasing the ability of lymphocytes to control tumor growth.
Multicenter study
The research has been coordinated from Navarrabiomed by Imanol Aroza’s from Martinicoresponsible for the Cancer Signaling Unitand is part of the doctoral thesis from the Public University of Navarra in Martha Redondo Munoz. It has been developed in collaboration with the Institute of Neurosciences (mixed center of the CSIC and Miguel Hernández University), together with researchers from the group Cellular Plasticity in Development and Diseaseas well as with IRB Barcelona.
“This study demonstrates that it is possible to pharmacologically reorganize the metabolism of the tumor cell to improve the effect of targeted therapies and immunotherapies”
Imanol Arozarena, principal investigator
From Navarrabiomed the research work was designed, as well as the experiments related to resistance to targeted therapies and the study of how ranolazine affects the immunogenicity of the melanoma cells.
“This study shows that it is possible rearrange pharmacologically he metabolism of the tumor cell to improve the effect of targeted therapies and immunotherapies. The next challenge is to demonstrate the clinical effect of these combinations in patients, as well as to study the potential of ranolazine in other types of cancer. To do this, we have to better understand how this drug acts both in tumor cells and in the immune system,” says Arozarena.
Immunotherapy tests with mice were developed at the Institute of Neurosciences and the study of immune cells of the tumor microenvironment.
“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 preclinical models of melanoma, which supports its possible application in patients”, highlights Berta Sanchez-Laorden.
Meanwhile, at IRB Barcelona the RNA sequencing analysis of individual cells, which have allowed us to know in detail the effect of ranolazine on the metabolic state of tumor cells.
Despite representing only 10% of skin cancer cases, melanoma is responsible for 90% of deaths associated with skin tumors
“We suspected that the fatty acid metabolism was crucial in the most aggressive forms of melanoma, but being able to confirm it with a drug already approved for use in humans is highly relevant,” he says. Aznar Benitah, who hopes that “these results could be the way to change clinical practice”.
Incidence
In the year 2022were diagnosed in Spain 7,500 new cases of cutaneous melanoma. Worldwide, this type of cancer accounts for 3.4% of the total cancer cases detected. Despite representing only 10% of skin cancer cases, melanoma is responsible for 90% of deaths associated with skin tumors.
Thanks to the appearance of targeted therapies and immunotherapies, the clinical treatment of people affected with melanoma has improved, but 50% of patients still do not respond and/or acquire resistance to these therapies. The combination of the current therapies with ranolazine could offer a therapeutic alternative for these patients, improving their clinical response.
This study has been possible thanks to the institutional support and funding granted by the Ministry of Science and Innovation, the Carlos III Health Institute, the government of Navarra, the Spanish Multidisciplinary Melanoma Group (GEM) and the Melanoma Research Alliance, among others.
Reference:
Redondo-Muñoz M, et al. “Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy”. Nature Metabolism (2023)
Rights: Creative Commons.
#drug #applied #cardiac #ailments #improve #efficacy #therapies #melanoma