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染色体外环状DNA的影响:一种在癌症耐药性中指导肿瘤发生的机制——综述

Impact of ecDNA: A mechanism that directs tumorigenesis in cancer drug Resistance-A review.

作者信息

Ashique Sumel, Upadhyay Aakash, Garg Ashish, Mishra Neeraj, Hussain Afzal, Negi Poonam, Hing Goh Bey, Bhatt Shvetank, Ali Md Khadem, Gowthamarajan Kuppusamy, Singh Sachin Kumar, Gupta Gaurav, Chellappan Dinesh Kumar, Dua Kamal

机构信息

Department of Pharmaceutics, Bharat Institute of Technology (BIT), School of Pharmacy, Meerut, Uttar Pradesh, 250103, India.

Department of P.G. Studies and Research in Chemistry and Pharmacy, Rani Durgavati University Jabalpur, M.P, 482001, India.

出版信息

Chem Biol Interact. 2022 Aug 25;363:110000. doi: 10.1016/j.cbi.2022.110000. Epub 2022 Jun 4.

Abstract

Extrachromosomal DNA (ecDNA) is often found in cancerous cells, and numerous scientific investigations have already shown that ecDNA-mediated oncogene amplification which contributes to cancer therapy resistance. This ecDNA is found to be essential for enhancing gene transcription and resistance to chemotherapeutic drugs, as well as promoting tumor heterogeneity and reversing tumor phenotypes, suggesting that it plays a key role in carcinogenesis. The ecDNA induces tumors to become hostile which results in a lower survival rate and chemotherapy tolerance. It also holds the potential as a target for treatment or diagnostic procedure of tumors. The review describes the properties and origins of ecDNA, as well as how it affects carcinogenesis, its function in cancer etiology and progression, and its therapeutic value. Propagation of oncogenes and resistance genes situated in extra-chromosomal DNA has been discovered to become one of the primary causes of intra-tumor genetic heterogeneity and may result in a threshold of probable evolutionary adaptation in many investigations.

摘要

染色体外DNA(ecDNA)常在癌细胞中发现,众多科学研究已表明,ecDNA介导的致癌基因扩增会导致癌症治疗耐药。已发现这种ecDNA对于增强基因转录和对化疗药物的耐药性至关重要,同时还能促进肿瘤异质性和逆转肿瘤表型,这表明它在致癌过程中起关键作用。ecDNA会使肿瘤变得具有侵袭性,从而导致较低的生存率和化疗耐受性。它还具有作为肿瘤治疗或诊断靶点的潜力。这篇综述描述了ecDNA的特性和起源,以及它如何影响致癌作用、在癌症病因和进展中的功能及其治疗价值。位于染色体外DNA中的致癌基因和耐药基因的传播已被发现是肿瘤内遗传异质性的主要原因之一,并且在许多研究中可能导致可能的进化适应阈值。

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