抗真菌药物再用于癌症治疗。
Repurposing antifungal drugs for cancer therapy.
机构信息
Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, PR China; Department of Medical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian 350011, PR China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China; Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
出版信息
J Adv Res. 2023 Jun;48:259-273. doi: 10.1016/j.jare.2022.08.018. Epub 2022 Sep 5.
BACKGROUND
Repurposing antifungal drugs in cancer therapy has attracted unprecedented attention in both preclinical and clinical research due to specific advantages, such as safety, high-cost effectiveness and time savings compared with cancer drug discovery. The surprising and encouraging efficacy of antifungal drugs in cancer therapy, mechanistically, is attributed to the overlapping targets or molecular pathways between fungal and cancer pathogenesis. Advancements in omics, informatics and analytical technology have led to the discovery of increasing "off-site" targets from antifungal drugs involved in cancerogenesis, such as smoothened (D477G) inhibition from itraconazole in basal cell carcinoma.
AIM OF REVIEW
This review illustrates several antifungal drugs repurposed for cancer therapy and reveals the underlying mechanism based on their original target and "off-site" target. Furthermore, the challenges and perspectives for the future development and clinical applications of antifungal drugs for cancer therapy are also discussed, providing a refresh understanding of drug repurposing.
KEY SCIENTIFIC CONCEPTS OF REVIEW
This review may provide a basic understanding of repurposed antifungal drugs for clinical cancer management, thereby helping antifungal drugs broaden new indications and promote clinical translation.
背景
由于与抗癌药物发现相比具有安全性、高成本效益和节省时间等特定优势，重新利用抗真菌药物进行癌症治疗在临床前和临床研究中引起了前所未有的关注。抗真菌药物在癌症治疗中的惊人和令人鼓舞的疗效在机制上归因于真菌和癌症发病机制之间重叠的靶点或分子途径。组学、信息学和分析技术的进步导致越来越多的与癌症发生相关的抗真菌药物的“非靶点”被发现，例如伊曲康唑在基底细胞癌中对 smoothened（D477G）的抑制作用。
综述目的
本文综述了几种重新用于癌症治疗的抗真菌药物，并根据其原始靶点和“非靶点”揭示了潜在的机制。此外，还讨论了抗真菌药物用于癌症治疗的未来发展和临床应用的挑战和前景，为药物再利用提供了新的认识。
综述的关键科学概念
本文可能为临床癌症管理中重新利用的抗真菌药物提供了基本的了解，从而帮助抗真菌药物拓宽新的适应症并促进临床转化。
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