通过DNA二级结构和CRISPR工具箱调节乳腺癌中的基因表达。

NAR Cancer Pub Date : 2021-12-01 DOI:10.1093/narcan/zcab048
Jessica A Kretzmann, Kelly L Irving, Nicole M Smith, Cameron W Evans
{"title":"通过DNA二级结构和CRISPR工具箱调节乳腺癌中的基因表达。","authors":"Jessica A Kretzmann,&nbsp;Kelly L Irving,&nbsp;Nicole M Smith,&nbsp;Cameron W Evans","doi":"10.1093/narcan/zcab048","DOIUrl":null,"url":null,"abstract":"<p><p>Breast cancer is the most commonly diagnosed malignancy in women, and while the survival prognosis of patients with early-stage, non-metastatic disease is ∼75%, recurrence poses a significant risk and advanced and/or metastatic breast cancer is incurable. A distinctive feature of advanced breast cancer is an unstable genome and altered gene expression patterns that result in disease heterogeneity. Transcription factors represent a unique therapeutic opportunity in breast cancer, since they are known regulators of gene expression, including gene expression involved in differentiation and cell death, which are themselves often mutated or dysregulated in cancer. While transcription factors have traditionally been viewed as 'undruggable', progress has been made in the development of small-molecule therapeutics to target relevant protein-protein, protein-DNA and enzymatic active sites, with varying levels of success. However, non-traditional approaches such as epigenetic editing, transcriptional control via CRISPR/dCas9 systems, and gene regulation through non-canonical nucleic acid secondary structures represent new directions yet to be fully explored. Here, we discuss these new approaches and current limitations in light of new therapeutic opportunities for breast cancers.</p>","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693572/pdf/","citationCount":"7","resultStr":"{\"title\":\"Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox.\",\"authors\":\"Jessica A Kretzmann,&nbsp;Kelly L Irving,&nbsp;Nicole M Smith,&nbsp;Cameron W Evans\",\"doi\":\"10.1093/narcan/zcab048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Breast cancer is the most commonly diagnosed malignancy in women, and while the survival prognosis of patients with early-stage, non-metastatic disease is ∼75%, recurrence poses a significant risk and advanced and/or metastatic breast cancer is incurable. A distinctive feature of advanced breast cancer is an unstable genome and altered gene expression patterns that result in disease heterogeneity. Transcription factors represent a unique therapeutic opportunity in breast cancer, since they are known regulators of gene expression, including gene expression involved in differentiation and cell death, which are themselves often mutated or dysregulated in cancer. While transcription factors have traditionally been viewed as 'undruggable', progress has been made in the development of small-molecule therapeutics to target relevant protein-protein, protein-DNA and enzymatic active sites, with varying levels of success. However, non-traditional approaches such as epigenetic editing, transcriptional control via CRISPR/dCas9 systems, and gene regulation through non-canonical nucleic acid secondary structures represent new directions yet to be fully explored. Here, we discuss these new approaches and current limitations in light of new therapeutic opportunities for breast cancers.</p>\",\"PeriodicalId\":18879,\"journal\":{\"name\":\"NAR Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693572/pdf/\",\"citationCount\":\"7\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NAR Cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/narcan/zcab048\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NAR Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/narcan/zcab048","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 7

摘要

乳腺癌是女性中最常见的恶性肿瘤,虽然早期非转移性疾病患者的生存预后约为75%,但复发的风险很大,晚期和/或转移性乳腺癌是无法治愈的。晚期乳腺癌的一个显著特征是不稳定的基因组和改变的基因表达模式,导致疾病异质性。转录因子代表了乳腺癌的独特治疗机会,因为它们是已知的基因表达调节剂,包括参与分化和细胞死亡的基因表达,而这些基因表达本身在癌症中经常发生突变或失调。虽然转录因子传统上被认为是“不可药物的”,但针对相关蛋白质-蛋白质、蛋白质- dna和酶活性位点的小分子疗法的开发已经取得了进展,并取得了不同程度的成功。然而,表观遗传编辑、通过CRISPR/dCas9系统进行转录调控、通过非典型核酸二级结构进行基因调控等非传统途径则是有待充分探索的新方向。在这里,我们讨论这些新的方法和目前的局限性,在新的治疗机会乳腺癌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox.

Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox.

Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox.

Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox.

Breast cancer is the most commonly diagnosed malignancy in women, and while the survival prognosis of patients with early-stage, non-metastatic disease is ∼75%, recurrence poses a significant risk and advanced and/or metastatic breast cancer is incurable. A distinctive feature of advanced breast cancer is an unstable genome and altered gene expression patterns that result in disease heterogeneity. Transcription factors represent a unique therapeutic opportunity in breast cancer, since they are known regulators of gene expression, including gene expression involved in differentiation and cell death, which are themselves often mutated or dysregulated in cancer. While transcription factors have traditionally been viewed as 'undruggable', progress has been made in the development of small-molecule therapeutics to target relevant protein-protein, protein-DNA and enzymatic active sites, with varying levels of success. However, non-traditional approaches such as epigenetic editing, transcriptional control via CRISPR/dCas9 systems, and gene regulation through non-canonical nucleic acid secondary structures represent new directions yet to be fully explored. Here, we discuss these new approaches and current limitations in light of new therapeutic opportunities for breast cancers.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信