三阴性乳腺癌作为一种特殊类型的难治性乳腺癌,其分子生物学特性比较独特,目前分子靶向治疗被广泛应用于该病的治疗中。在刚刚结束的第39届圣安东尼奥乳腺癌研讨会上,来自美国南加州大学的Alexander Ring研究员展示了一项有关三阴性乳腺癌中分子靶点的研究成果。
编者按:三阴性乳腺癌作为一种特殊类型的难治性乳腺癌,其分子生物学特性比较独特,目前分子靶向治疗被广泛应用于该病的治疗中。在刚刚结束的第39届圣安东尼奥乳腺癌研讨会上,来自美国南加州大学的Alexander Ring研究员展示了一项有关三阴性乳腺癌中分子靶点的研究成果(The role of CBP/FOXM1 in triple negative breast cancer,摘要号:P3-07-10),本刊特邀Alexander Ring进行了现场解读。
Alexander Ring:The idea of the poster was to identify a molecular target in triple-negative breast cancer. The work we have been doing has basically been leveraging a so-called chemical-genomic approach to identify such a target. We used a small molecule inhibitor called ICG-001, which is a specific CBP binding molecule and tested this first in cell line models to see what effect this small molecule has on triple-negative breast cancer. Through gene and protein expression studies, we found that a potential target in triple-negative breast cancer is FOXM1. We validated these initial studies by further gene expression studies and genetic knockdowns and also phenotype studies to see if targeting FOXM1 in triple-negative breast cancer has an effect on drug resistance in this highly aggressive breast cancer phenotype. We can show in in vitro models and in in vivo xenograft models from patients that potentially targeting FOXM1 in triple-negative breast cancer could result in a therapeutic benefit for patients with this disease.
Alexander Ring:壁报展示的内容是确定三阴性乳腺癌的分子靶点。我们一直在做的工作基本上是利用所谓的化学基因组方法来确定这样的靶点。我们使用一种称为ICG-001的小分子抑制剂,其是CBP特异性结合分子,并且首先在细胞系模型中测试这种抑制剂以观察该小分子对三阴性乳腺癌具有什么影响。通过基因和蛋白质表达研究,我们发现三阴性乳腺癌的潜在靶点是FOXM1。再通过进一步的基因表达研究和基因敲除以及表型研究来验证这些初始研究,以确定三阴性乳腺癌中靶向FOXM1是否对这种高度侵袭性乳腺癌表型的耐药性具有影响。体外模型和体内异种移植模型研究结果显示,潜在靶向FOXM1在三阴性乳腺癌治疗中可以为患者带来获益。