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Under hypoxic conditions, common to growing tumours, VGSCs develop a persistent current (I\n                      <jats:sub>NaP<\/jats:sub>\n                      ) which can be blocked selectively by ranolazine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-024-02622-w","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T04:03:43Z","timestamp":1709179423000},"page":"1415-1419","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels"],"prefix":"10.1038","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1435-8540","authenticated-orcid":false,"given":"Mustafa B. 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