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重新利用代谢调节剂:抗糖尿病药物作为抗癌剂。

Repurposing metabolic regulators: antidiabetic drugs as anticancer agents.

机构信息

Rhenix Lifesciences, Hyderabad, 500038, Telangana, India.

CureScience, 5820 Oberlin Dr, Suite 202, San Diego, CA, 92121, USA.

出版信息

Mol Biomed. 2024 Sep 28;5(1):40. doi: 10.1186/s43556-024-00204-z.


DOI:10.1186/s43556-024-00204-z
PMID:39333445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11436690/
Abstract

Drug repurposing in cancer taps into the capabilities of existing drugs, initially designed for other ailments, as potential cancer treatments. It offers several advantages over traditional drug discovery, including reduced costs, reduced development timelines, and a lower risk of adverse effects. However, not all drug classes align seamlessly with a patient's condition or long-term usage. Hence, repurposing of chronically used drugs presents a more attractive option. On the other hand, metabolic reprogramming being an important hallmark of cancer paves the metabolic regulators as possible cancer therapeutics. This review emphasizes the importance and offers current insights into the repurposing of antidiabetic drugs, including metformin, sulfonylureas, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), thiazolidinediones (TZD), and α-glucosidase inhibitors, against various types of cancers. Antidiabetic drugs, regulating metabolic pathways have gained considerable attention in cancer research. The literature reveals a complex relationship between antidiabetic drugs and cancer risk. Among the antidiabetic drugs, metformin may possess anti-cancer properties, potentially reducing cancer cell proliferation, inducing apoptosis, and enhancing cancer cell sensitivity to chemotherapy. However, other antidiabetic drugs have revealed heterogeneous responses. Sulfonylureas and TZDs have not demonstrated consistent anti-cancer activity, while SGLT2 inhibitors and DPP-4 inhibitors have shown some potential benefits. GLP-1RAs have raised concerns due to possible associations with an increased risk of certain cancers. This review highlights that further research is warranted to elucidate the mechanisms underlying the potential anti-cancer effects of these drugs and to establish their efficacy and safety in clinical settings.

摘要

药物重定位在癌症中利用了现有药物的能力,这些药物最初是为其他疾病设计的,作为潜在的癌症治疗方法。它相对于传统的药物发现具有几个优势,包括降低成本、缩短开发时间和降低不良反应风险。然而,并非所有药物类别都能与患者的病情或长期使用完全匹配。因此,重新利用慢性使用的药物是一个更具吸引力的选择。另一方面,代谢重编程是癌症的一个重要标志,为代谢调节剂作为潜在的癌症治疗方法铺平了道路。本综述强调了重新利用抗糖尿病药物的重要性,并提供了当前对抗糖尿病药物(包括二甲双胍、磺酰脲类药物、钠-葡萄糖共转运蛋白 2(SGLT2)抑制剂、二肽基肽酶 4(DPP-4)抑制剂、胰高血糖素样肽-1 受体激动剂(GLP-1RAs)、噻唑烷二酮(TZD)和α-葡萄糖苷酶抑制剂)的重新利用的见解,针对各种类型的癌症。调节代谢途径的抗糖尿病药物在癌症研究中受到了相当大的关注。文献揭示了抗糖尿病药物与癌症风险之间的复杂关系。在抗糖尿病药物中,二甲双胍可能具有抗癌特性,可能降低癌细胞增殖、诱导细胞凋亡,并增强癌细胞对化疗的敏感性。然而,其他抗糖尿病药物的反应则不一致。磺酰脲类药物和 TZD 没有表现出一致的抗癌活性,而 SGLT2 抑制剂和 DPP-4 抑制剂则显示出一些潜在的益处。GLP-1RAs 引起了人们的关注,因为它们可能与某些癌症风险增加有关。本综述强调需要进一步研究,以阐明这些药物潜在抗癌作用的机制,并确定它们在临床环境中的疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/93fd1b948ba2/43556_2024_204_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/51e4b66a1fb4/43556_2024_204_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/4b830e7f6a28/43556_2024_204_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/4ba438b71428/43556_2024_204_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/93fd1b948ba2/43556_2024_204_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/51e4b66a1fb4/43556_2024_204_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/4b830e7f6a28/43556_2024_204_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/4ba438b71428/43556_2024_204_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78d/11436690/93fd1b948ba2/43556_2024_204_Fig4_HTML.jpg

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[6]
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本文引用的文献

[1]
Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes.

JAMA Netw Open. 2024-7-1

[2]
Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies.

Eur J Pharmacol. 2024-9-5

[3]
Diabetes and Cancer: A Twisted Bond.

Oncol Rev. 2024-5-21

[4]
The impact of surgery and oncological treatment on risk of type 2 diabetes onset in patients with colorectal cancer: nationwide cohort study in Denmark.

Elife. 2024-6-3

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Drug repurposing for cancer therapy.

Signal Transduct Target Ther. 2024-4-19

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Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence.

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Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect.

Transl Oncol. 2024-6

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Novel Antidiabetic Drugs and the Risk of Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

J Clin Med. 2024-3-20

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