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从驱虫到癌症治疗:血液系统恶性肿瘤中的苯并咪唑类药物

From Deworming to Cancer Therapy: Benzimidazoles in Hematological Malignancies.

作者信息

Golla Upendarrao, Patel Satyam, Shah Nyah, Talamo Stella, Bhalodia Riya, Claxton David, Dovat Sinisa, Sharma Arati

机构信息

Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

出版信息

Cancers (Basel). 2024 Oct 12;16(20):3454. doi: 10.3390/cancers16203454.

Abstract

Drug repurposing is a strategy to discover new therapeutic uses for existing drugs, which have well-established toxicity profiles and are often more affordable. This approach has gained significant attention in recent years due to the high costs and low success rates associated with traditional drug development. Drug repositioning offers a more time- and cost-effective path for identifying new treatments. Several FDA-approved non-chemotherapy drugs have been investigated for their anticancer potential. Among these, anthelmintic benzimidazoles (such as albendazole, mebendazole, and flubendazole) have garnered interest due to their effects on microtubules and oncogenic signaling pathways. Blood cancers, which frequently develop resistance and have high mortality rates, present a critical need for effective therapies. This review highlights the recent advances in repurposing benzimidazoles for blood malignancies. These compounds induce cell cycle arrest, differentiation, tubulin depolymerization, loss of heterozygosity, proteasomal degradation, and inhibit oncogenic signaling to exert their anticancer effects. We also discuss current limitations and strategies to overcome them, emphasizing the potential of combining benzimidazoles with standard therapies for improved treatment of hematological cancers.

摘要

药物重新利用是一种为现有药物发现新治疗用途的策略,这些药物具有已明确的毒性特征且通常价格更为低廉。由于传统药物研发成本高昂且成功率低,这种方法近年来受到了广泛关注。药物重新定位为确定新治疗方法提供了一条更具时间和成本效益的途径。几种已获美国食品药品监督管理局(FDA)批准的非化疗药物已被研究其抗癌潜力。其中,驱虫苯并咪唑类药物(如阿苯达唑、甲苯达唑和氟苯达唑)因其对微管和致癌信号通路的作用而引起了关注。血癌经常产生耐药性且死亡率高,对有效治疗方法有着迫切需求。本综述重点介绍了将苯并咪唑类药物重新用于治疗血液恶性肿瘤的最新进展。这些化合物可诱导细胞周期停滞、分化、微管蛋白解聚、杂合性缺失、蛋白酶体降解,并抑制致癌信号传导以发挥其抗癌作用。我们还讨论了当前的局限性以及克服这些局限性的策略,强调了将苯并咪唑类药物与标准疗法联合使用以改善血液癌症治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c54/11506385/9b1a08e996f6/cancers-16-03454-g001.jpg

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