Abstract
To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties. A review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it was tested with this purpose in the experimental and clinical settings. The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole. Each of them are independently described and analyzed. The above mentioned pharmaceuticals have shown anti-metastatic and anti-invasion activity and many of them deserve to be tested in well-planned clinical trials as adjunct therapies for solid tumors and as anti-metastatic agents. Antiepileptic drugs like phenytoin, carbamazepine and valproate and the vasodilator flunarizine emerged as particularly useful for anti-metastatic purposes.
Highlights
The capacity to metastasize is one of the hallmarks of cancer1 and usually death due to cancer is not caused by the primary tumor but rather by the metastatic spread2
Tetrodotoxin (TTX) Many biological toxins like those found in scorpions and sea anemones develop their toxicity by introducing modifications to the properties of VGSCs52
This toxicity can be achieved by inactivation of voltage-gated sodium channel (VGSC) or on the contrary by persistent activation of the channel
Summary
The capacity to metastasize is one of the hallmarks of cancer and usually death due to cancer is not caused by the primary tumor but rather by the metastatic spread. The lack of an effective therapy in prevention of metastasis results in a high mortality rate in oncology. It seems reasonable that if the risk of metastasis can be reduced, the outlook of cancer patients may significantly improve survival and quality of life. Solving the metastasis problem is solving the cancer problem. Like genistein, resveratrol and curcumin have shown interesting anti-metastasis activity. The same effect has been observed with older pharmaceuticals like aspirin, not-as-old pharmaceuticals such as celecoxib; new pharmaceuticals like ticagrelor, as well as with more sophisticated molecules like dasatinib and ponatinib or ultrasophisticated drugs, like polymeric plerixafor
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