From HDAC to Voltage-Gated Ion Channels: What’s Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer

Abstract

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients’ outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs have also been reported as molecular targets through which antiepileptic drugs (AEDs) seem to exert their anticancer activity. This should be claimed as a great advantage. Indeed, due to the slowness of drug approval procedures, the attempt to turn to off-label use of already approved medicines would be highly preferable. Therefore, an updated and accurate overview of both preclinical and clinical data of commonly prescribed AEDs (mainly valproic acid, lamotrigine, carbamazepine, phenytoin and gabapentin) in breast, prostate, brain and other cancers will follow. Finally, a glance at the emerging attempt to administer AEDs by means of opportunely designed drug delivery systems (DDSs), so to limit toxicity and improve bioavailability, is also given.

A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery

“…Due to the lack of sufficient data, severe adverse reactions like delirium could not be assessed. Additionally, the gabapentin class of drugs, especially at higher doses, may affect the metastatic progression of tumor cells through disruption of Ca2 + signaling in Mat-LyLu cells in prostate cancer [ 52 , 53 ]. Even if the available data are largely controversial and inadequate at present, the use of pregabalin warrants caution [ 53 ].…”

“…Additionally, the gabapentin class of drugs, especially at higher doses, may affect the metastatic progression of tumor cells through disruption of Ca2 + signaling in Mat-LyLu cells in prostate cancer [ 52 , 53 ]. Even if the available data are largely controversial and inadequate at present, the use of pregabalin warrants caution [ 53 ]. Consequently, the findings impaired the plausibility of using preemptive pregabalin in cancer-related surgery.…”

The influence of different excipients on Valproic acid tablets in neurological disorder treatment

“…Excessive calcium influx into neurons can trigger various neurotoxic processes, including excitotoxicity and apoptosis, leading to neuronal injury and cell death. VPA mitigates these neurotoxic effects by reducing calcium influx through L-type channels, protecting neurons from damage and promoting neuronal survival [30] .…”

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

“…Recently, it was shown that VPA exerts an inhibitory effect on histone deacetylation. This, together with its ability to block the voltage-gated Na + and Ca ++ channels, both of which are considered tumor markers, has prompted the suggestion of its use in breast, prostate, and other types of cancers [113].…”