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通过靶向代谢改变和上皮-间质转化途径利用药物重新利用来对抗乳腺癌

Harnessing Drug Repurposing to Combat Breast Cancer by Targeting Altered Metabolism and Epithelial-to-Mesenchymal Transition Pathways.

作者信息

Kandasamy Thirukumaran, Sarkar Shilpi, Ghosh Siddhartha Sankar

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati-39, Assam India.

Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati-39, Assam India.

出版信息

ACS Pharmacol Transl Sci. 2024 Oct 31;7(12):3780-3794. doi: 10.1021/acsptsci.4c00545. eCollection 2024 Dec 13.

Abstract

Breast cancer remains one of the most prevalent and challenging cancers to treat due to its complexity and heterogenicity. Cellular processes such as metabolic reprogramming and epithelial-to-mesenchymal transition (EMT) contribute to the complexity of breast cancer by driving uncontrolled cell division, metastasis, and resistance to therapies. Strategically targeting these intricate pathways can effectively impede breast cancer progression, thereby revealing significant potential for therapeutic interventions. Among various emerging therapeutic approaches, drug repurposing offers a promising avenue for enhancing clinical outcomes. In recent years, high-throughput screening, QSAR, and network pharmacology have been widely employed to identify promising repurposed drugs. As an outcome, several drugs, such as Metformin, Itraconazole, Pimozide, and Disulfiram, were repurposed to regulate metabolic and EMT pathways. Moreover, strategies such as combination therapy, targeted delivery, and personalized medicine were utilized to enhance the efficacy and specificity of the repurposed drugs. This review focuses on the potential of targeting altered metabolism and EMT in breast cancer through drug repurposing. It also highlights recent advancements in drug screening techniques, associated limitations, and strategies to overcome these challenges.

摘要

由于其复杂性和异质性,乳腺癌仍然是最难治疗的常见癌症之一。代谢重编程和上皮-间质转化(EMT)等细胞过程通过驱动不受控制的细胞分裂、转移和对治疗的抗性,导致了乳腺癌的复杂性。从战略上针对这些复杂的途径可以有效地阻碍乳腺癌的进展,从而显示出治疗干预的巨大潜力。在各种新兴的治疗方法中,药物重新利用为改善临床结果提供了一条有前景的途径。近年来,高通量筛选、定量构效关系(QSAR)和网络药理学已被广泛用于识别有前景的重新利用药物。结果,几种药物,如二甲双胍、伊曲康唑、匹莫齐特和双硫仑,被重新用于调节代谢和EMT途径。此外,联合治疗、靶向递送和个性化医疗等策略被用于提高重新利用药物的疗效和特异性。本综述重点关注通过药物重新利用靶向乳腺癌中改变的代谢和EMT的潜力。它还强调了药物筛选技术的最新进展、相关局限性以及克服这些挑战的策略。

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