摘要
三阴性乳腺癌(TNBC)是由雌激素受体(ER),孕激素受体(PR),和缺乏表达或扩增人表皮生长因子受体2(HER2)所定义的。TNBC的临床病理特点是高分级,高细胞增殖率和更大程度的染色体重排。三阴性乳腺癌患者更可能耐药并且治疗更加困难,并且还经常BRCA1突变。BRCA1基因启动子区的甲基化与减少BRCA1 mRNA水平相关。有BRCA1基因甲基化的TNBC患者与非甲基化的基因相比有更好的无病生存期。从治疗的角度来说,BRCA1基因的表达水平对不同类的化疗有着重要的决定因素。BRCA1功能性肿瘤对DNA损伤的化疗药物如铂类药物过敏。虽然铂类药物是目前广泛使用的在乳腺癌化疗中传统的化疗药物,但是他们的使用有几个缺点。因此,十分令人感兴趣的是可以寻求作为替代的治疗金属为基础的化合物,以克服这些铂类药物的局限性。钌基化合物可能是最有前途的替代铂类药物。本文综述了作为预测指标,以及抗癌钌化合物的一个潜在的药物靶标基因的使用。
关键词: BRCA1;三阴性乳腺癌(TNBC);钌配合物。
Current Cancer Drug Targets
Title:BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds
Volume: 16 Issue: 7
Author(s): Khwanjira Hongthong and Adisorn Ratanaphan
Affiliation:
关键词: BRCA1;三阴性乳腺癌(TNBC);钌配合物。
摘要: Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). The clinicopathological characteristics of TNBC include a high grading, a high rate of cell proliferation and a greater degree of chromosomal rearrangement. Patients with triple-negative breast cancer are more likely to be drug resistant and more difficult to treat, and are also frequently BRCA1 mutants. Methylation of the BRCA1 promoter region is associated with a reduction of the BRCA1 mRNA level. TNBC patients with a methylated BRCA1 had a better disease-free survival compared with those with non-methylated BRCA1. From a therapeutic perspective, the expression level of BRCA1 has been a major determinant of the responses to different classes of chemotherapy. BRCA1-dysfunctional tumors are hypersensitive to DNA damaging chemotherapeutic agents like platinum drugs. Although platinum based drugs are currently widely used as conventional chemotherapeutic drugs in breast cancer chemotherapy, their use has several disadvantages. It is therefore of interest to seek out alternative therapeutic metal-based compounds that could overcome the limitations of these platinum based drugs. Ruthenium-based compounds could be the most promising alternative to the platinum drugs. This review highlights the use of BRCA1 as a predictive marker as well as for a potential drug target for anticancer ruthenium compounds.
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Khwanjira Hongthong and Adisorn Ratanaphan , BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds, Current Cancer Drug Targets 2016; 16 (7) . https://dx.doi.org/10.2174/1568009616666160203113957
DOI https://dx.doi.org/10.2174/1568009616666160203113957 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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