Glénisson Mathilde, Vacher Sophie, Callens Céline, Susini Aurélie, Cizeron-Clairac Géraldine, Le Scodan Romuald, Meseure Didier, Lerebours Florence, Spyratos Frédérique, Lidereau Rosette, Bièche Ivan
Laboratory of Oncogenetic, Institut Curie, Hôpital René Huguenin, St-Cloud, France.
Genes Cancer. 2012 Jan;3(1):63-70. doi: 10.1177/1947601912449832.
Triple-negative breast cancer (TNBC) is a subgroup of breast cancer that is negative for estrogen and progesterone receptor and ERBB2 protein expression. It is characterized by its aggressive behavior and by the lack of targeted therapies. To identify new therapeutic targets in TNBC, we used real-time quantitative RT-PCR to analyze 63 TNBC samples in terms of their mRNA expression of 26 genes coding for the major proteins currently targeted by drugs used to treat other cancers or undergoing clinical trials in breast cancer. Six of the 26 genes tested (VEGFA, SRC, PARP1, PTK2, RAF1, and FGFR3) were significantly upregulated in 13% to 46% of the TNBCs. None of the 6 genes was specifically upregulated in the TNBCs compared with 3 other classical breast tumor subtypes. No association was observed between overexpression of these 6 genes (except for FGFR3) and PIK3CA mutation status. These results confirm the interest of targeting VEGFA and PARP1 in ongoing clinical trials in TNBC patients and also identify new target genes (SRC, PTK2, RAF1, and FGFR3). Clinical trials could be initiated easily with existing drugs. Our results also suggest that these target genes might serve as predictive biomarkers of the TNBC treatment response.
三阴性乳腺癌（TNBC）是乳腺癌的一个亚组，其雌激素和孕激素受体以及ERBB2蛋白表达均为阴性。它的特点是侵袭性强且缺乏靶向治疗方法。为了在TNBC中鉴定新的治疗靶点，我们使用实时定量逆转录聚合酶链反应（RT-PCR）分析了63个TNBC样本中26个基因的mRNA表达情况，这些基因编码的主要蛋白质目前是用于治疗其他癌症的药物靶点或正在乳腺癌临床试验中的靶点。在检测的26个基因中，有6个基因（VEGFA、SRC、PARP1、PTK2、RAF1和FGFR3）在13%至46%的TNBC中显著上调。与其他3种经典乳腺癌亚型相比，这6个基因在TNBC中均未特异性上调。除FGFR3外，未观察到这6个基因的过表达与PIK3CA突变状态之间存在关联。这些结果证实了在TNBC患者正在进行的临床试验中靶向VEGFA和PARP1的意义，同时也鉴定出了新的靶基因（SRC、PTK2、RAF1和FGFR3）。利用现有药物可以轻松启动临床试验。我们的结果还表明，这些靶基因可能作为TNBC治疗反应的预测生物标志物。
