SBIR TOPIC 283 PHASE I - DEVELOPMENT OF A MOLECULAR DIAGNOSTIC ASSAY TO DETECT B

一种基于免疫组织化学检测特征蛋白生物标记物的分子诊断试验将被开发用于诊断基底细胞样乳腺癌(BLBC)，类似于已经在乳腺癌中检测雌激素受体和人类表皮生长因子受体2(HER2)的常规使用的方法。该分析将基于使用一种新的用于福尔马林固定的石蜡包埋的乳腺肿瘤组织的新型单抗来检测转录因子FOXC1蛋白。FOXC1最近被我们的小组证明是一种具有特征性的、高度特异的BLBC组织水平生物标记物。FOXC1也是一个潜在的治疗靶点，因为它在协调侵袭性癌症特征方面发挥了关键作用。这项建议的重点是论证和建立这样一种准确检测BLBC的分子诊断方法的概念验证。成功完成这项第一阶段研究是在第二阶段进行这项诊断测试的大规模临床验证之前至关重要的。如果成功验证，基于FOXC1蛋白表达的分子诊断测试将极大地简化常规临床实践中的BLBC诊断，因为拟议的测试系统成本低，易于与现有的临床病理实践相结合。

A molecular diagnostic test based on immunohistochemical detection of a characteristic protein biomarker will be developed to diagnose basal-like breast cancer (BLBC), similar to those already in routine use for detection of estrogen receptor and human epidermal growth factor receptor 2 (HER2) in breast cancer. The assay will be based on the detection of transcription factor FOXC1 protein utilizing a novel monoclonal antibody optimized for use on formalin-fixed paraffin-embedded breast tumor tissue. FOXC1 has recently been demonstrated by our group to be a characteristic, highly specific tissue level biomarker of BLBC. FOXC1 is also a potential therapeutic target by virtue of its demonstrated critical role in coordinating aggressive cancer traits. This proposal is focused on demonstrating and establishing the proof-of-concept of such a molecular diagnostic assay for the accurate detection of BLBC. Successful completion of this Phase I study is essential prior to undertaking large scale clinical validation of this diagnostic test in Phase II. If successfully validated, the molecular diagnostic test based on FOXC1 protein expression would greatly simplify the diagnosis of BLBC in routine clinical practice owing to the low cost and ease of integration of the proposed testing system into currently existing clinical pathology practice.