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

Thirukumaran Kandasamy, Shilpi Sarkar and Siddhartha Sankar Ghosh*, 
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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.

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利用靶向改变代谢和上皮-间质转化途径的药物再利用来对抗乳腺癌
由于乳腺癌的复杂性和异质性,它仍然是最普遍和最具挑战性的癌症之一。细胞过程如代谢重编程和上皮-间质转化(EMT)通过驱动不受控制的细胞分裂、转移和对治疗的抵抗,增加了乳腺癌的复杂性。有策略地靶向这些复杂的通路可以有效地阻止乳腺癌的进展,从而揭示了治疗干预的重大潜力。在各种新兴的治疗方法中,药物再利用为提高临床结果提供了一条有希望的途径。近年来,高通量筛选、QSAR和网络药理学被广泛应用于识别有前途的再用途药物。因此,一些药物,如二甲双胍、伊曲康唑、吡莫齐和双硫仑,被重新用于调节代谢和EMT途径。此外,采用联合治疗、靶向给药和个性化用药等策略来提高药物的疗效和特异性。本文综述了通过药物再利用靶向改变乳腺癌代谢和EMT的潜力。它还强调了药物筛选技术的最新进展、相关限制和克服这些挑战的策略。
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来源期刊
ACS Pharmacology and Translational Science
ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)
CiteScore
10.00
自引率
3.30%
发文量
133
期刊介绍: ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.
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