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表观遗传修饰:癌症异质性和耐药性的关键因素

Epigenetic modifications: Key players in cancer heterogeneity and drug resistance.

作者信息

Sadida Hana Q, Abdulla Alanoud, Marzooqi Sara Al, Hashem Sheema, Macha Muzafar A, Akil Ammira S Al-Shabeeb, Bhat Ajaz A

机构信息

Laboratory of Precision Medicine in Diabetes, Obesity and Cancer, Department of Population Genetics, Sidra Medicine, Doha 26999, Qatar.

Laboratory of Genomic Medicine, Department of Population Genetics, Sidra Medicine, Doha 26999, Qatar.

出版信息

Transl Oncol. 2024 Jan;39:101821. doi: 10.1016/j.tranon.2023.101821. Epub 2023 Nov 4.

Abstract

Cancer heterogeneity and drug resistance remain pivotal obstacles in effective cancer treatment and management. One major contributor to these challenges is epigenetic modifications - gene regulation that does not involve changes to the DNA sequence itself but significantly impacts gene expression. As we elucidate these phenomena, we underscore the pivotal role of epigenetic modifications in regulating gene expression, contributing to cellular diversity, and driving adaptive changes that can instigate therapeutic resistance. This review dissects essential epigenetic modifications - DNA methylation, histone modifications, and chromatin remodeling - illustrating their significant yet complex contributions to cancer biology. While these changes offer potential avenues for therapeutic intervention due to their reversible nature, the interplay of epigenetic and genetic changes in cancer cells presents unique challenges that must be addressed to harness their full potential. By critically analyzing the current research landscape, we identify knowledge gaps and propose future research directions, exploring the potential of epigenetic therapies and discussing the obstacles in translating these concepts into effective treatments. This comprehensive review aims to stimulate further research and aid in developing innovative, patient-centered cancer therapies. Understanding the role of epigenetic modifications in cancer heterogeneity and drug resistance is critical for scientific advancement and paves the way towards improving patient outcomes in the fight against this formidable disease.

摘要

癌症异质性和耐药性仍然是有效治疗和管理癌症的关键障碍。造成这些挑战的一个主要因素是表观遗传修饰,即不涉及DNA序列本身变化但会显著影响基因表达的基因调控。在我们阐释这些现象时,我们强调了表观遗传修饰在调节基因表达、促成细胞多样性以及驱动适应性变化(这些变化可能引发治疗抗性)方面的关键作用。本综述剖析了重要的表观遗传修饰——DNA甲基化、组蛋白修饰和染色质重塑——阐明了它们对癌症生物学的重大但复杂的贡献。虽然这些变化因其可逆性提供了潜在的治疗干预途径,但癌细胞中表观遗传和基因变化的相互作用带来了独特的挑战,要充分发挥它们的潜力就必须加以解决。通过批判性地分析当前的研究状况,我们找出了知识空白并提出了未来的研究方向,探索表观遗传疗法的潜力,并讨论将这些概念转化为有效治疗方法过程中存在的障碍。这篇全面的综述旨在激发进一步的研究,并有助于开发创新的、以患者为中心的癌症治疗方法。了解表观遗传修饰在癌症异质性和耐药性中的作用对于科学进步至关重要,并为改善抗击这种可怕疾病的患者预后铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/10654239/ba99960f4cf5/ga1.jpg

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