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依非韦伦:癌症治疗的新希望。

Efavirenz: New Hope in Cancer Therapy.

作者信息

Elango Varshitha Dheep, Mugundan Uma Maheshwari, Mg Rajanandh

机构信息

Department of Pharmacy Practice, SRM (Sri Ramasamy Memorial) College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Kattankulathur, IND.

出版信息

Cureus. 2024 Aug 25;16(8):e67776. doi: 10.7759/cureus.67776. eCollection 2024 Aug.

DOI:10.7759/cureus.67776
PMID:39323697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11422744/
Abstract

Despite extensive research directed at preventive and treatment strategies, breast cancer remains the leading cause of cancer-related mortality among women. This necessitates the development of a new medication aimed at increasing patient survival and quality of life. A new drug's development from the ground up can cost billions of dollars and take up to ten or more years. Because much of the required safety and pharmacokinetic data are already available from earlier trials, repurposing medications usually results in lower costs and shorter turnaround times. Many antiretroviral medications target biological pathways and enzymes associated with cancer, which becomes an ideal option for repurposing as anticancer medications. Efavirenz is an antiretroviral medication that targets molecular pathways implicated in the growth of breast cancer, such as LINE-1 (long interspersed nuclear elements-1) suppression, hence lowering the proliferation of breast cancer cells and exhibiting anti-cancer properties. Additionally, it suppresses the fatty acid synthase gene and other important genes related to fat metabolism, impairing mitochondrial activity and making cancer cells deprived of energy. Efavirenz also inhibits cancer-initiating stem cells, promotes differentiation, and prevents recurrence. Additionally, efavirenz promotes oxidative damage by the formation of superoxide in cancer cells. In addition to its anti-cancer properties, efavirenz has the advantage of being a well-established and relatively inexpensive medication with a favorable safety profile. If proven effective, efavirenz could offer a cost-effective therapeutic option, which is an intriguing direction that warrants further investigation.

摘要

尽管针对预防和治疗策略进行了广泛研究,但乳腺癌仍是女性癌症相关死亡的主要原因。这就需要研发一种旨在提高患者生存率和生活质量的新药。从头开发一种新药可能耗资数十亿美元,耗时长达十年甚至更久。由于许多所需的安全性和药代动力学数据已可从早期试验中获得,因此药物重新利用通常会降低成本并缩短周转时间。许多抗逆转录病毒药物靶向与癌症相关的生物途径和酶,这使其成为重新用作抗癌药物的理想选择。依非韦伦是一种抗逆转录病毒药物,靶向与乳腺癌生长相关的分子途径,如LINE-1(长散在核元件-1)抑制,从而降低乳腺癌细胞的增殖并表现出抗癌特性。此外,它还抑制脂肪酸合酶基因和其他与脂肪代谢相关的重要基因,损害线粒体活性,使癌细胞缺乏能量。依非韦伦还抑制癌症起始干细胞,促进分化并防止复发。此外,依非韦伦通过在癌细胞中形成超氧化物来促进氧化损伤。除了其抗癌特性外,依非韦伦还具有已被充分证实、相对便宜且安全性良好的优势。如果被证明有效,依非韦伦可以提供一种具有成本效益的治疗选择,这是一个值得进一步研究的有趣方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b47e/11422744/2f4182f1227b/cureus-0016-00000067776-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b47e/11422744/2f4182f1227b/cureus-0016-00000067776-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b47e/11422744/2f4182f1227b/cureus-0016-00000067776-i01.jpg

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本文引用的文献

1
Targeted Therapy and Mechanisms of Drug Resistance in Breast Cancer.乳腺癌的靶向治疗与耐药机制
Cancers (Basel). 2023 Feb 19;15(4):1320. doi: 10.3390/cancers15041320.
2
Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.二甲双胍/依非韦伦/氟西汀通过癌细胞特异性 ROS 扩增表现出显著的抗癌活性。
Cancer Biol Ther. 2023 Dec 31;24(1):20-32. doi: 10.1080/15384047.2022.2161803.
3
Efavirenz as a potential drug for the treatment of triple-negative breast cancers.
依非韦伦作为一种治疗三阴性乳腺癌的潜在药物。
Clin Transl Oncol. 2021 Feb;23(2):353-363. doi: 10.1007/s12094-020-02424-5. Epub 2020 Jun 21.
4
When fats commit crimes: fatty acid metabolism, cancer stemness and therapeutic resistance.当脂肪犯罪时:脂肪酸代谢、癌症干性和治疗抵抗。
Cancer Commun (Lond). 2018 Jul 11;38(1):47. doi: 10.1186/s40880-018-0317-9.
5
Cytotoxic effect of Efavirenz in BxPC-3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation.依非韦伦对BxPC-3胰腺癌细胞的细胞毒性作用基于氧化应激,且与电离辐射具有协同作用。
Oncol Lett. 2018 Feb;15(2):1728-1736. doi: 10.3892/ol.2017.7523. Epub 2017 Dec 5.
6
and polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.并且多态性与接受R-CHOP治疗的弥漫性大B细胞淋巴瘤患者的临床结局相关。
Oncotarget. 2017 Apr 6;8(35):58292-58303. doi: 10.18632/oncotarget.16869. eCollection 2017 Aug 29.
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LINE-1 as a therapeutic target for castration-resistant prostate cancer.作为治疗去势抵抗性前列腺癌的靶点的 LINE-1。
Front Biosci (Landmark Ed). 2018 Jan 1;23(7):1292-1309. doi: 10.2741/4644.
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