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二氯乙酸 (DCA) 与癌症:临床应用概述。

Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications.

机构信息

Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), 85028, Italy.

Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71121, Italy.

出版信息

Oxid Med Cell Longev. 2019 Nov 14;2019:8201079. doi: 10.1155/2019/8201079. eCollection 2019.

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.

摘要

大量文献描述了二氯乙酸(DCA)的抗癌特性,但将其有效应用于癌症治疗的临床实践仍然局限于临床试验。神经毒性等副作用的发生以及对 DCA 致癌性的怀疑仍然限制了 DCA 的临床应用。然而,近年来,越来越多的报告支持 DCA 在癌症治疗中的应用,这也是因为人们对靶向肿瘤细胞代谢产生了浓厚的兴趣。解析 DCA 的作用机制有助于理解其对癌细胞选择性疗效的基础。DCA 与常规化疗、放疗、其他药物或天然化合物联合应用已在多种癌症模型中进行了测试。新的药物递送系统和包含 DCA 及其他药物的多作用化合物似乎通过多种药物的协同作用改善了生物利用度,并表现出更高的效率。越来越多的报告支持 DCA 在癌症治疗中的有效性,促使人们进行了更多的研究,从而发现了 DCA 的其他潜在分子靶点。有趣的是,DCA 可能会显著影响癌症干细胞的比例,有助于癌症的消除。总的来说,这些发现为 DCA 在癌症治疗中的临床转化研究提供了强有力的依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce9/6885244/3887c15aa60c/OMCL2019-8201079.001.jpg

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