Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.
Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.
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在世界范围内，乳腺癌是妇女最常诊断的癌症之一，也是妇女癌症相关死亡的第二大原因。虽然肿瘤遗传学有助于治疗乳腺癌和告知患者预后的疗法，但组蛋白蛋白的修饰（有助于将细胞中的遗传物质组织成染色质）也会影响治疗反应和最终的患者结局。在这里，我们探讨的作用，修改组蛋白的酶在乳腺癌。我们讨论了这些可逆的，或“表观遗传”，染色质的变化如何扰乱肿瘤环境，并描述了临床前研究，为靶向乳腺癌染色质修饰酶提供了理论基础。我们基于现有的临床前数据，将表观遗传活性与支持致癌生长的细胞变化联系起来，并在适用时评估靶向乳腺癌染色质修饰酶治疗的当前临床状态。乳腺癌的发病机制、治疗和患者结局取决于肿瘤内在基因组改变，这些改变将乳腺肿瘤分为分子亚型。这些分子亚型通常决定可行的治疗干预措施，并最终决定患者的结局。然而，治疗反应的异质性可能是潜在的表观遗传学特征的结果，这些特征可能进一步分层乳腺癌患者的结局。在这篇综述中，我们研究了驱动乳腺癌染色质功能变化的非遗传机制，以促进细胞和肿瘤的适应性，并强调表观遗传活性如何为治疗反应提供信息。最后，我们提供了前景的治疗靶向表观遗传酶，一种方法，具有未开发的潜力，以改善乳腺癌患者的结果。
Worldwide, breast cancer is among the most frequently diagnosed cancers in women and the second leading cause of cancer-associated mortality in women. While tumor genetics contribute to therapies used to treat breast cancer and inform patient prognosis, modifications of histone proteins, which help organize the genetic material in cells into chromatin, can also influence therapeutic response and ultimately patient outcome. Here, we explore the role of enzymes that modify histone proteins in breast cancer. We discuss how these reversible, or “epigenetic”, changes to chromatin perturb the tumor environment and describe preclinical studies that provide a rationale for targeting chromatin-modifying enzymes in breast cancer. We build on existing preclinical data to connect epigenetic activity with changes in cells that support oncogenic growth and, when applicable, assess the current clinical status of treatments that target chromatin-modifying enzymes in breast cancer. Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigenetic activity may inform the therapeutic response. We conclude by providing perspectives on the future of therapeutic targeting of epigenetic enzymes, an approach that holds untapped potential to improve breast cancer patient outcomes.
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DOI：
10.1111/j.1349-7006.2001.tb02153.x
发表时间：
2001-12
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Choi JH;Kwon HJ;Yoon BI;Kim JH;Han SU;Joo HJ;Kim DY
通讯作者：
Kim DY
雌激素受体阳性乳腺癌的新型致癌增强剂
DOI：
10.1016/j.omtn.2022.08.029
发表时间：
2022-09-13
期刊：
MOLECULAR THERAPY NUCLEIC ACIDS
影响因子：
--
作者：
Bao, Chunjie;Duan, Jialun;Xie, Ying;Liu, Yixuan;Li, Peishan;Li, Jianwei;Zhao, Huihui;Guo, Haitao;Men, Yanchen;Ren, Yuxin;Xu, Jiarui;Wang, Guiling;Lu, Wanliang
通讯作者：
Lu, Wanliang
影响因子：
12.4
作者：
Bassi C;Li YT;Khu K;Mateo F;Baniasadi PS;Elia A;Mason J;Stambolic V;Pujana MA;Mak TW;Gorrini C
通讯作者：
Gorrini C
影响因子：
4.8
作者：
Chowdhury, Sanjib;Howell, Gillian M.;Brattain, Michael G.
通讯作者：
Brattain, Michael G.
他莫昔芬在乳腺癌中的分子机制和模式。
影响因子：
1.9
作者：
Ali S;Rasool M;Chaoudhry H;N Pushparaj P;Jha P;Hafiz A;Mahfooz M;Abdus Sami G;Azhar Kamal M;Bashir S;Ali A;Sarwar Jamal M
通讯作者：
Sarwar Jamal M