Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels
Menée à partir de données épidémiologiques et de données issues d'études précliniques, cette étude examine le potentiel antimétastatique de la ranozaline, une molécule ciblant les canaux sodiques dépendants du voltage
Background : Multi-faceted evidence from a range of cancers suggests strongly that de novo expression of voltage-gated sodium channels (VGSCs) plays a significant role in driving cancer cell invasiveness. Under hypoxic conditions, common to growing tumours, VGSCs develop a persistent current (INaP) which can be blocked selectively by ranolazine. Methods : Several different carcinomas were examined. We used data from a range of experimental approaches relating to cellular invasiveness and metastasis. These were supplemented by survival data mined from cancer patients. Results : In vitro, ranolazine inhibited invasiveness of cancer cells especially under hypoxia. In vivo, ranolazine suppressed the metastatic abilities of breast and prostate cancers and melanoma. These data were supported by a major retrospective epidemiological study on breast, colon and prostate cancer patients. This showed that risk of dying from cancer was reduced by ca.60% among those taking ranolazine, even if this started 4 years after the diagnosis. Ranolazine was also shown to reduce the adverse effects of chemotherapy on heart and brain. Furthermore, its anti-cancer effectiveness could be boosted by co-administration with other drugs. Conclusions : Ranolazine, alone or in combination with appropriate therapies, could be reformulated as a safe anti-metastatic drug offering many potential advantages over current systemic treatment modalities.