聚腺苷酸二磷酸核糖转移酶-1抑制剂在三阴性乳腺癌中的应用现状

Current application status of Poly(ADP-ribose)polymerase-1 Inhibitors in triple negative breast cancer

目的对国内外聚腺苷酸二磷酸核糖转移酶-1[Poly(ADP-ribose)polymerase-1,PARP1]抑制剂在三阴性乳腺癌中的应用现状进行综述分析。方法应用PubMed及CNKI期刊全文数据库检索系统,以"聚腺苷酸二磷酸核糖转移酶-1、PARP1抑制剂、三阴性乳腺癌"等为关键词,检索2009-01-2014-02相关文献,共检索到英文文献322条,中文文献201条。纳入标准:1)PARP1分子的生物学功能;2)PARP1抑制剂在BRCA突变相关乳腺癌以及三阴性乳腺癌方面的基础与临床研究;剔除标准:1)PARP1抑制剂的药理学特性;2)PARP1与乳腺癌发生相关性研究。最后纳入分析33篇文献。结果 "合成致死"原理是PARP1抑制剂在BRCA突变相关乳腺癌中发挥抗肿瘤活性的理论基础,PARP1抑制剂治疗BRCA突变相关的乳腺癌的Ⅰ、Ⅱ临床试验取得良好的成果,但是在三阴性乳腺癌的治疗方面,Ⅲ期临床试验并未得到预期的试验结果,在应用PARP1抑制剂之前重组修复通路的功能状态以及PARP1的活性应该得到合理评估。结论三阴性乳腺癌与BRCA突变相关乳腺癌存在表型的相似性,但是三阴性乳腺癌患者是否可以受益于PARP1抑制剂的治疗,还需要进一步深入研究,同时寻找可靠生物标记分子预测PARP1抑制剂治疗的敏感性,是目前PARP1抑制剂应用于临床所面临的挑战。

OBJECTIVE To review the current application status of PARP1 inhibitors in triple negative breast cancer.METHODS ＂Poly（ADP-ribose）polymerase-1;PARP1inhibitors;and triple negative breast cancer＂were used as key words and searched for literatures published between January 2009 to Febreuary 2014 in Pubmed and CNKI data-bases.Totally 322 English literatures and 201 Chinese literatures were retrieved.Choice criteria：Molecular biological function of PARP1;Basic and clinical research of PARP1 inhibitors in BRCA mutation-related breast cancer as well as triple negative breast cancer.Exclusion criteria：Pharmacological properties of PARP1inhibitors;Research of the correlation between PARP1 and breast cancer occurrence.A total of 33 articles meeting the criteria were used for analysis.RESULTS ＂Synthetic lethal＂principle was the theoretical basis for anti-tumor activity of PARP1 inhibitors in breast cancer with BRCA mutations.Phase Ⅰ/Ⅱ trials indicated PARP inhibitor had promise activity in BRCA mutations-related breast cancer.However,in triple negative breast cancer treatment,phaseⅢ clinical trials did not get the expected results.Recombination repair pathway functional status and PARP1 activity should be reasonably assessed before applying PARP1 inhibitors.CONCLUSIONS Although there are phenotype similarities between triple negative breast cancer and BRCAmutations-related breast cancer,whether triple negative breast cancer patients can benefit from treatment PARP1 inhibitors also needs further study.Looking for reliable biomarkers to predict sensitivity to PARP1 inhibitor therapy remains a challenge for the clinical.