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PARP抑制剂在乳腺癌治疗中的研究进展
作者: PARP抑制剂在乳腺癌治疗中的研究进展
Authors: Li Yuan, Wang Zhongzhao, Xuan Lixue
单位: 国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院乳腺外科100021
Units: Department of Breast Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
关键词: 乳腺肿瘤;聚ADP核糖聚合酶类;酶抑制剂;研究进展
Keywords: Breast neoplasms;Poly(ADPribose) polymerases;Enzyme Inhibitors;Research progress
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出版年,卷(期):页码:2020,47(1):40-45
摘要:

 有乳腺癌易感基因(BRCA)胚系突变的个体患乳腺癌的风险显著增加,且BRCA突变癌细胞的DNA同源重组修复存在异常。无论是由于BRCA1/2基因突变,还是由于其他信号通路的异常所引起同源重组异常的乳腺癌,均可通过抑制聚腺苷二磷酸核糖聚合酶(PARP)取得显著疗效。随着多种PARP抑制剂通过美国食品药品监督管理局审批用于治疗卵巢癌患者,多项临床试验也正在评估PARP抑制剂单药或联合治疗是否可以使更多乳腺癌患者获益。除PARP抑制剂单药治疗对乳腺癌患者的研究外,还有PARP抑制剂铂类药物联合治疗携带BRCA基因突变乳腺癌或三阴性乳腺癌的研究。此外,很多关于免疫疗法联合PARP抑制剂治疗乳腺癌的研究也正在进行中。然而PARP抑制剂毒性及治疗抵抗的问题仍然存在。本文对PARP抑制剂在乳腺癌中的临床治疗和亟待解决的问题进行讨论,并对其发展前景作一展望。

 Individuals with breast cancer susceptibility genes(BRCA) germline mutations have a significantly increased lifetime risk for breast cancer,BRCAmutant cancer cells have abnormal homologous recombination repair of DNA.Inhibition of Poly (ADPribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Currently, under U.S.Food and Drug Administration approval of PARP inhibitor on ovarian cancer, clinical trials for PARP inhibitor are being conducted to assess whether PARP inhibitor as monotherapy or in combination with other drugs could benefit more breast cancer patients. Besides the studies of PARP inhibitor as monotherapy in breast cancer patients, researches in investigating platinumPARP inhibitor combination in BRCA mutated breast cancer or triple negative breast cancer were conducted. In addition, many studies of immunotherapy combined with PARP inhibitor in breast cancer are ongoing. However, resistance to PARP inhibitors and the toxicity of the drugs remain challenges. This review will discuss the utility and unsolved problems of PARP inhibitor in breast cancer as well as the potential future directions.    

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