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他汀类药物作为抗肿瘤药物:重新定位药物的范例。

Statins as anti-tumor agents: A paradigm for repurposed drugs.

机构信息

Laboratory of Chromatin Biology & Epigenetics, Indian Institute of Science Education and Research, Pune, India.

Centre of Excellence in Epigenetics, Department of Life Sciences, Shiv Nadar Institution of Eminence, Gautam Buddha Nagar, India.

出版信息

Cancer Rep (Hoboken). 2024 May;7(5):e2078. doi: 10.1002/cnr2.2078.

Abstract

BACKGROUND

Statins, frequently prescribed medications, work by inhibiting the rate-limiting enzyme HMG-CoA reductase (HMGCR) in the mevalonate pathway to reduce cholesterol levels. Due to their multifaceted benefits, statins are being adapted for use as cost-efficient, safe and effective anti-cancer treatments. Several studies have shown that specific types of cancer are responsive to statin medications since they rely on the mevalonate pathway for their growth and survival.

RECENT FINDINGS

Statin are a class of drugs known for their potent inhibition of cholesterol production and are typically prescribed to treat high cholesterol levels. Nevertheless, there is growing interest in repurposing statins for the treatment of malignant neoplastic diseases, often in conjunction with chemotherapy and radiotherapy. The mechanism behind statin treatment includes targeting apoptosis through the BCL2 signaling pathway, regulating the cell cycle via the p53-YAP axis, and imparting epigenetic modulations by altering methylation patterns on CpG islands and histone acetylation by downregulating DNMTs and HDACs respectively. Notably, some studies have suggested a potential chemo-preventive effect, as decreased occurrence of tumor relapse and enhanced survival rate were reported in patients undergoing long-term statin therapy. However, the definitive endorsement of statin usage in cancer therapy hinges on population based clinical studies with larger patient cohorts and extended follow-up periods.

CONCLUSIONS

The potential of anti-cancer properties of statins seems to reach beyond their influence on cholesterol production. Further investigations are necessary to uncover their effects on cancer promoting signaling pathways. Given their distinct attributes, statins might emerge as promising contenders in the fight against tumorigenesis, as they appear to enhance the efficacy and address the limitations of conventional cancer treatments.

摘要

背景

他汀类药物是一种常用的处方药物,通过抑制甲羟戊酸途径中的限速酶 HMG-CoA 还原酶(HMGCR)来降低胆固醇水平。由于其多方面的益处,他汀类药物正被用于开发成本效益高、安全有效的抗癌治疗方法。多项研究表明,由于某些类型的癌症依赖于甲羟戊酸途径来生长和存活,因此它们对他汀类药物治疗有反应。

最近的发现

他汀类药物是一类以强效抑制胆固醇生成而闻名的药物,通常用于治疗高胆固醇血症。然而,人们越来越有兴趣将他汀类药物重新用于治疗恶性肿瘤疾病,通常与化疗和放疗联合使用。他汀类药物治疗的机制包括通过 BCL2 信号通路靶向细胞凋亡,通过 p53-YAP 轴调节细胞周期,以及通过改变 CpG 岛的甲基化模式和分别下调 DNMTs 和 HDACs 来改变组蛋白乙酰化来进行表观遗传调节。值得注意的是,一些研究表明他汀类药物治疗可能具有化学预防作用,因为接受长期他汀类药物治疗的患者肿瘤复发发生率降低,生存率提高。然而,他汀类药物在癌症治疗中的使用是否得到明确认可,取决于基于人群的临床研究,这些研究需要更大的患者队列和更长的随访期。

结论

他汀类药物的抗癌特性的潜力似乎超出了其对胆固醇生成的影响。需要进一步的研究来揭示它们对促进癌症的信号通路的影响。鉴于其独特的特性,他汀类药物可能成为对抗肿瘤发生的有前途的竞争者,因为它们似乎可以提高疗效,并解决传统癌症治疗的局限性。

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