Cortellesi Elisa, Savini Isabella, Veneziano Matteo, Gambacurta Alessandra, Catani Maria Valeria, Gasperi Valeria
Department of Experimental Medicine, Tor Vergata University of Rome, 00133 Rome, Italy.
NAST Centre (Nanoscience & Nanotechnology & Innovative Instrumentation), Tor Vergata University of Rome, 00133 Rome, Italy.
Int J Mol Sci. 2025 Mar 13;26(6):2605. doi: 10.3390/ijms26062605.
Breast cancer (BC) is the most prevalent malignancy among women, characterized by extensive heterogeneity stemming from molecular and genetic alterations. This review explores the intricate epigenetic landscape of BC, highlighting the significant role of epigenetic modifications-particularly DNA methylation, histone modifications, and the influence of non-coding RNAs-in the initiation, progression, and prognosis of the disease. Epigenetic alterations drive crucial processes, including gene expression regulation, cell differentiation, and tumor microenvironment interactions, contributing to tumorigenesis and metastatic potential. Notably, aberrations in DNA methylation patterns, including global hypomethylation and hypermethylation of CpG islands, have been associated with distinct BC subtypes, with implications for early detection and risk assessment. Furthermore, histone modifications, such as acetylation and methylation, affect cancer cell plasticity and aggressiveness by profoundly influencing chromatin dynamics and gene transcription. Finally, non-coding RNAs contribute by modulating epigenetic machinery and gene expression. Despite advances in our knowledge, clinical application of epigenetic therapies in BC is still challenging, often yielding limited efficacy when used alone. However, combining epi-drugs with established treatments shows promise for enhancing therapeutic outcomes. This review underscores the importance of integrating epigenetic insights into personalized BC treatment strategies, emphasizing the potential of epigenetic biomarkers for improving diagnosis, prognosis, and therapeutic response in affected patients.
乳腺癌(BC)是女性中最常见的恶性肿瘤,其特征是由分子和基因改变导致的广泛异质性。本综述探讨了乳腺癌复杂的表观遗传格局,强调了表观遗传修饰——特别是DNA甲基化、组蛋白修饰以及非编码RNA的影响——在该疾病的发生、发展和预后中的重要作用。表观遗传改变驱动着关键过程,包括基因表达调控、细胞分化和肿瘤微环境相互作用,促进肿瘤发生和转移潜能。值得注意的是,DNA甲基化模式的异常,包括整体低甲基化和CpG岛的高甲基化,与不同的乳腺癌亚型相关,对早期检测和风险评估具有重要意义。此外,组蛋白修饰,如乙酰化和甲基化,通过深刻影响染色质动力学和基因转录来影响癌细胞的可塑性和侵袭性。最后,非编码RNA通过调节表观遗传机制和基因表达发挥作用。尽管我们在知识方面取得了进展,但表观遗传疗法在乳腺癌中的临床应用仍然具有挑战性,单独使用时往往疗效有限。然而,将表观遗传药物与既定治疗方法相结合显示出改善治疗效果的前景。本综述强调了将表观遗传见解整合到个性化乳腺癌治疗策略中的重要性,强调了表观遗传生物标志物在改善受影响患者的诊断、预后和治疗反应方面的潜力。