Abstract
An extensive body of literature describes anticancer property of dichloroacetate (DCA), but its effective clinical administration in cancer therapy is still limited to clinical trials. The occurrence of side effects such as neurotoxicity as well as the suspicion of DCA carcinogenicity still restricts the clinical use of DCA. However, in the last years, the number of reports supporting DCA employment against cancer increased also because of the great interest in targeting metabolism of tumour cells. Dissecting DCA mechanism of action helped to understand the bases of its selective efficacy against cancer cells. A successful coadministration of DCA with conventional chemotherapy, radiotherapy, other drugs, or natural compounds has been tested in several cancer models. New drug delivery systems and multiaction compounds containing DCA and other drugs seem to ameliorate bioavailability and appear more efficient thanks to a synergistic action of multiple agents. The spread of reports supporting the efficiency of DCA in cancer therapy has prompted additional studies that let to find other potential molecular targets of DCA. Interestingly, DCA could significantly affect cancer stem cell fraction and contribute to cancer eradication. Collectively, these findings provide a strong rationale towards novel clinical translational studies of DCA in cancer therapy.
Highlights
Cancer is one of the leading causes of death worldwide
Salts of DCA selectively target cancer cells shifting their metabolism from glycolysis to oxidative phosphorylation by inhibition of pyruvate dehydrogenase kinase (PDK), the inhibitor of pyruvate dehydrogenase (PDH) [10]
A study performed in non-smallcell lung cancer (NSCLC) showed both in vitro and in vivo that coadministration of DCA with paclitaxel increased the efficiency of cell death through autophagy inhibition [32]
Summary
Cancer is one of the leading causes of death worldwide. Despite the significant progression in diagnostic and therapeutic approaches, its eradication still represents a challenge. We recently described DCA ability to affect mitochondrial function and retarding cancer progression in a pancreatic cancer model [12]. Consistent data from clinical trials and case reports describing DCA administration in cancer patients are available [13,14,15,16], but, despite the growing body of literature sustaining the efficacy of. This review is aimed at summarizing the very recent reports suggesting the employment of DCA in cancer therapy, in combination with chemotherapy agents, radiotherapy, and other chemical or natural compounds showing anticancer properties. We described data about new purposed pharmacological formulations of DCA able to avoid side effects and ameliorate drug bioavailability and efficacy, further encouraging its possible clinical employment. We reviewed latest findings suggesting other potential mechanisms of action of DCA, including new data about its aptitude to affect cancer stem cell fraction
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