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基于基因组学视角的乳腺癌化疗耐药机制研究进展

Advances in the study of chemotherapy resistance mechanisms in breast cancer based on genomics perspective

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【作者】 蔡凌翼; 陈涛; 张晓琳; 李哲媛; 张牛霖; 孔令奇; 史尚莹; 张菁桠; 杜福泉; 郝晶;

【Author】 CAI Lingyi;CHEN Tao;ZHANG Xiaolin;LI Zheyuan;ZHANG Niulin;KONG Lingqi;SHI Shangying;ZHANG Jingya;DU Fuquan;HAO JING;The First Clinical School of Medicine,Heilongjiang University of Chinese Medicine;

【通讯作者】 郝晶;

【机构】 黑龙江中医药大学第一临床医学院; 黑龙江中医药大学研究生院; 黑龙江中医药大学附属第一医院血液病科;

【摘要】 乳腺癌(BC)于2020年首次成为全球患病率最高的癌症,是女性常见的癌症之一。乳腺癌作为一种生长迅速的浸润性癌症,严重威胁全球女性的健康。目前,乳腺癌的主要治疗手段为化学治疗,然而伴随着相关药物(主要包括紫杉醇、蒽环类和铂类)的使用,由于膜转运体、凋亡诱导与自噬诱导的化学抗性、DNA损伤修复能力增强、肿瘤微环境等因素出现了多药耐药问题。多药耐药(MDR)是导致乳腺癌患者预后差的重要原因之一。因此探索多药耐药相关的分子机制,找到对应的耐药关键基因一直是临床研究热点之一。已有很多研究表明,ATP结合盒转运蛋白(本文重点论述ABCB1、ABCC与ABCG2)、谷胱甘肽-S-转肽酶(GST-π)、拓扑异构酶Ⅱ(TOPOⅡ)、长非编码RNA(LncRNA)、含半胱氨酸的天冬氨酸蛋白水解酶3(CASP3)等基因与乳腺癌化疗耐药密切相关。本研究对乳腺癌化疗耐药基因相关的文献进行回顾和系统综述,并且基于现有耐药机制的相关研究,探讨应对乳腺癌化疗耐药的有效策略,为今后化疗耐药靶向治疗的研究提供一定的参考。

【Abstract】 Breast cancer, which became the cancer with the highest prevalence rate in the world for the first time in 2020, is one of the most common cancers in women. As a fast-growing invasive cancer, breast cancer has become a serious threat to women’s health worldwide. Currently, the mainstay of breast cancer treatment is chemotherapy, however, along with the use of related drugs(mainly including paclitaxel, anthracyclines, and platinums), the problem of multidrug resistance has arisen due to membrane transporters, apoptosis-induced and autophagy-induced chemoresistance, enhanced DNA damage repair, and the tumor microenvironment. Multidrug resistance is one of the major causes of poor prognosis in breast cancer patients. Therefore, exploring the molecular mechanisms related to multidrug resistance and finding the corresponding key genes for drug resistance has been one of the hotspots of clinical research. Many studies have shown that ATP-binding cassette transporter proteins(this article focuses on ABCB1, ABCC and ABCG2) are involved in multidrug resistance, glutathione-S-transferase(GST-π), topoisomerase Ⅱ(TOPO Ⅱ), long non-coding RNA(LncRNA) and cysteine-containing aspartic acid protein hydrolase 3(CASP3) are genes closely associated with chemoresistance in breast cancer. In this study, we systematically reviewed the literature related to chemoresistance genes in breast cancer, and explored the effective strategies to deal with breast cancer chemoresistance based on the existing studies on the mechanism of chemoresistance, so as to provide some references for the research on chemoresistance-targeted therapies in the future.

【关键词】 乳腺癌; 基因; 耐药; 化疗; 治疗;
【Key words】 Breast cancer; Genes; Drug resistance; Chemotherapy; Treatment;
【基金】 黑龙江省中医药科研课题项目(ZHY19-029)
  • 【文献出处】 中华全科医学 ,Chinese Journal of General Practice , 编辑部邮箱 ,2023年12期
  • 【分类号】R737.9
  • 【下载频次】181
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