三阴性乳腺癌靶向治疗的研究前景

Molecular targeted therapy in triple-negative breast cancer

目的分析三阴性乳腺癌(triple-negative breast cancer,TNBC)患者分子靶向治疗研究现状,对其前景予以展望。方法应用PubMed及CNKI期刊全文数据库检索系统,以"三阴性乳腺癌和靶向治疗"等为关键词,检索2006-01-2014-01的相关文献,共检索到英文文献1 477条,中文文献915条。纳入标准:1)TNBC的生物学特征;2)TNBC相关靶点的研究;3)TNBC相关靶向药物的研究及在诊治中的应用研究。根据纳入标准符合分析的文献49篇。结果临床前相关研究已经确定了几个潜在的靶点。TNBC中EGFR过度表达是其特征之一,EGFR下调蛋白PTEN表达的显著缺失是其预后差的一个重要因素;MET与basal/TN乳腺癌的诱导和进展有关,在basal like细胞系中MET和MET磷酸化均表现为较高水平;在basal/TNBC中SRC蛋白水平显著表达;大多数TNBC存在BRCA1的突变,从而导致DNA损伤修复缺陷。吉非替尼、西妥昔单抗和拉帕替尼、达沙替尼、Veliparib等药物已经应用于TNBC的临床治疗或者进入临床研究阶段,其临床效果目前尚缺乏有效数据支持。NOTCH1、VEGF、IGFR-1、ADAM17等潜在的靶点仍需要继续深入研究。结论与乳腺癌其他亚型不同,目前TNBC还缺少有效的靶向治疗。相关临床研究已经确定了EGFR、SRC、MET和PARP-1/2等潜在靶点。而NOTCH1、VEGF、IGFR-1和ADAM17等潜在的靶点仍需要继续深入研究。

OBJECTIVE To summarize the current status of the molecular targeted therapy in triple-negative breast cancer （TNBC）. METHODS From PubMed, Foreign Medical Journal database and CNKI periodical full text database retrieval system, related papers were searched using the keywords ＂TNBC, targeted therapy＂ from January 2006 to Januar- y 2014. Totally 1 477 English avticles and 915 Chinese articles were got. Retrieval criteria： 1）TNBC general characteris- tics;2）recent progress of TNBC target＇ research; 3）application in the diagnosis and treatment of the targeted drugs re- searches. 49 articles meeting the criteria were used for analysis. RESULTS Preclinical studies have identified several poten- tial targets. EGFR~ overexpression inTNBC is one of its characteristics, the loss of PTEN expression was significantly the prog- nosis of an important factor; MET is associated with the basal/TN breast cancer induction and progression of breast cancer, MET and MET phosphorylation showed higher levels; SRC protein expression levels are significantly in the basal/TNBC; The BRCA1 shows mutation in most of TNBC, resulting in DNA damage repair defects. The drugs, such as Gefitinib, Cetuximab, Lapatinb, Dasatinib, Veliparib, etc, have been applied in the clinical treatment of TNBC or entered into the phase of clinical re- search. Its clinical effect is lack of effective data support. And potential targets still need further research, such as NOTCH1, VEGF, IGFR-1, ADAM17, etc. CONCLUSIONS Unlike other subtypes of breast cancer,TNBC still lacks effective targeted ther- apy. Relevant clinical research studies have identified several potential targets, such as EGFR, SRC, MET, PARP-1/2, etc. And potential targets still need further research, such as NOTCH1, VEGF, IGFR-1, ADAM17, etc.