乳腺癌微环境中的表观遗传失调:对肿瘤进展和治疗策略的影响

IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Lenka Trnkova , Verona Buocikova , Michal Mego , Andrea Cumova , Monika Burikova , Martin Bohac , Svetlana Miklikova , Marina Cihova , Bozena Smolkova
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引用次数: 0

摘要

乳腺癌在女性癌症诊断中占很大比例,也是导致癌症相关死亡的主要原因。虽然对激素有反应的病例通常预后良好,但三阴性乳腺癌的侵袭性带来了挑战,对既有治疗方法的内在抗药性是一个长期存在的问题。获得性抗药性的出现加剧了这一复杂性,使乳腺癌的治疗更加复杂。表观遗传学变化,包括 DNA 甲基化、组蛋白和 RNA 修饰以及非编码 RNA,被认为是导致乳腺癌异质性的关键因素。肿瘤微环境(TME)中的每种细胞成分都具有独特的表观遗传结构,这使得影响治疗反应的复杂调控变得更加多样化。肿瘤微环境是一个由细胞和非细胞元素组成的复杂生态系统,与肿瘤细胞相互作用,形成免疫抑制微环境,并促进肿瘤生长、血管生成和细胞外基质重塑等过程。这些因素通过营造缺氧环境、诱导新陈代谢压力以及为药物输送制造物理障碍,为癌症治疗带来了挑战性条件。本文深入探讨了乳腺癌治疗反应、潜在的表观遗传学变化和 TME 内重要的相互作用之间的复杂联系。为了恢复对治疗的敏感性,文章强调需要考虑到TME中各个成员特有的表观遗传变化,采取综合疗法。认识到表观遗传学在耐药性中的关键作用并理解乳腺 TME 的特异性对于制定更有效的治疗策略至关重要。开发可靠的生物标志物对患者进行分层将有助于采用量身定制的精确治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Epigenetic deregulation in breast cancer microenvironment: Implications for tumor progression and therapeutic strategies

Epigenetic deregulation in breast cancer microenvironment: Implications for tumor progression and therapeutic strategies

Breast cancer comprises a substantial proportion of cancer diagnoses in women and is a primary cause of cancer-related mortality. While hormone-responsive cases generally have a favorable prognosis, the aggressive nature of triple-negative breast cancer presents challenges, with intrinsic resistance to established treatments being a persistent issue. The complexity intensifies with the emergence of acquired resistance, further complicating the management of breast cancer. Epigenetic changes, encompassing DNA methylation, histone and RNA modifications, and non-coding RNAs, are acknowledged as crucial contributors to the heterogeneity of breast cancer. The unique epigenetic landscape harbored by each cellular component within the tumor microenvironment (TME) adds great diversity to the intricate regulations which influence therapeutic responses. The TME, a sophisticated ecosystem of cellular and non-cellular elements interacting with tumor cells, establishes an immunosuppressive microenvironment and fuels processes such as tumor growth, angiogenesis, and extracellular matrix remodeling. These factors contribute to challenging conditions in cancer treatment by fostering a hypoxic environment, inducing metabolic stress, and creating physical barriers to drug delivery. This article delves into the complex connections between breast cancer treatment response, underlying epigenetic changes, and vital interactions within the TME. To restore sensitivity to treatment, it emphasizes the need for combination therapies considering epigenetic changes specific to individual members of the TME. Recognizing the pivotal role of epigenetics in drug resistance and comprehending the specificities of breast TME is essential for devising more effective therapeutic strategies. The development of reliable biomarkers for patient stratification will facilitate tailored and precise treatment approaches.

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来源期刊
CiteScore
11.90
自引率
2.70%
发文量
1621
审稿时长
48 days
期刊介绍: Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.
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