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Updated: Jul 1, 2025
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels
1Department of Life Sciences, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. m.djamgoz@imperial.ac.uk.
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.
Insights
Ranolazine effectively inhibits cancer cell invasion and metastasis, particularly under hypoxia. This drug may reduce cancer mortality by approximately 60% and offers potential as a safe anti-metastatic therapy.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Voltage-gated sodium channels (VGSCs) are increasingly implicated in driving cancer cell invasiveness.
- Hypoxia, common in tumors, promotes a persistent sodium current (INaP) via VGSCs.
- Ranolazine selectively blocks this INaP current.
Purpose of the Study:
- To investigate the anti-metastatic potential of ranolazine in various cancer types.
- To evaluate the efficacy of ranolazine in preclinical models and patient data.
- To assess ranolazine's impact on chemotherapy side effects.
Main Methods:
- In vitro assays examining cancer cell invasiveness under hypoxic conditions.
- In vivo studies assessing metastasis in breast cancer, prostate cancer, and melanoma models.
- Retrospective epidemiological analysis of survival data from breast, colon, and prostate cancer patients.
Main Results:
- Ranolazine significantly inhibited cancer cell invasiveness in vitro, especially under hypoxia.
- In vivo, ranolazine suppressed metastasis in multiple cancer types.
- Patient data revealed a ~60% reduction in cancer mortality risk for ranolazine users, with benefits observed even when initiated years post-diagnosis.
- Ranolazine also mitigated chemotherapy-induced cardiotoxicity and neurotoxicity.
Conclusions:
- Ranolazine demonstrates significant anti-metastatic properties and potential for reducing cancer mortality.
- It may serve as a safe alternative or adjunct to current systemic cancer therapies.
- Combination therapy with ranolazine could enhance anti-cancer effectiveness.
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