Triple Negative Breast Cancer: Novel Biomarkers and Therapeutic Strategies

非裔美国女性不成比例地受到三阴性乳腺癌 (TNBC) 的影响，三阴性乳腺癌是乳腺癌的一种形式 不表达三种广泛使用的生物标志物和治疗靶点的乳腺癌，即 Her-2、雌激素受体和孕激素受体。因此，这些妇女并没有从 针对这三种生物标志物的新疗法（例如赫赛汀疗法）。 TNBC 非常激进，导致 非裔美国妇女的死亡率高于其他人群的妇女。虽然 TNBC 最初 这些女性对化疗敏感，在没有替代治疗方案的情况下产生化疗耐药性 可用。因此，迫切需要识别 TNBC 的新型生物标志物并开发特异性的 消除这种健康差异的治疗策略。在初步研究中，我们已经鉴定出膜联蛋白 A2 作为 TNBC 的假定生物标志物。当 Her-2 呈阴性时，我们发现膜联蛋白 A2 表达显着 Her-2 过表达时，膜联蛋白 A2 表达减少；相反，当 Her-2 过表达时，膜联蛋白 A2 表达减少。 我们假设 AnxA2 过度表达导致非洲 TNBC 的高发 美国女性，AnxA2 是 TNBC 的有用生物标志物和治疗靶点。我们将测试这个 通过以下具体目标提出假设： 1) 将 TNBC 作为教育的重点纳入持续的教育中 针对高 nsk AA 女性的一级预防计划，2) 建立 AnxA2 的相关性 TNBC 患者中病理、预后变量和种族较差的表达，并验证 AnxA2 作为 TNBC 患者的诊断生物标志物。 3) 描绘 AnxA2-EGFR 介导的下游信号传导 TNBC 中调节癌细胞增殖、迁移和侵袭的途径，以及 4) 建立 AnxA2 作为三阴性乳腺癌的治疗靶点。 我们的期望是，成功完成拟议的工作将确定一个特定的生物标志物 新型治疗策略可以针对 TNBC。拟议的调查将有助于 了解 AnxA2 表达在不同种族群体 TNBC 发病率中的作用。

African-American women are disproportionately affected by triple negative breast cancer (TNBC), a form of breast cancer that does not express the three widely used biomarkers and therapeutic targets, namely Her-2, estrogen receptor and progesterone receptor. Consequently, these women do not benefit from the novel therapies (eg., Herceptin therapy) targeting the three biomarkers. TNBC are very aggressive, resulting in higher mortality rate in African-American women than women in other population. While TNBC is initially sensitive to chemotherapy, these women develop chemoresistance with no alternative treatment regimen available. Thus, there is a critical need to identify novel biomarkers for TNBC and develop specific therapeutic strategies to combat this health disparity. In preliminary studies, we have identified annexin A2 as a putative biomarker for TNBC. When Her-2 is negative, we find annexin A2 expression to be significantly increased, and conversely when Her-2 is overexpressed, annexin A2 expression is decreased. We hypothesize that AnxA2 overexpression accounts for the disproportionate occurrence of TNBC in African American women, and that AnxA2 is a useful biomarker and therapeutic target for TNBC. We will test this hypothesis through the following specific aims: 1) To integrate TNBC as a focus of education in an ongoing primary prevention program targeting high nsk AA women, 2) To establish the correlation of AnxA2 expression with poor pathological, prognostic variables and ethnicity in TNBC patients, and validate AnxA2 as a diagnostic biomarker for TNBC patients. 3) To delineate AnxA2-EGFR mediated downstream signaling pathway which regulates cancer cell proliferation, migration and invasion in TNBC, and 4) To establish AnxA2 as a therapeutic target in triple negative breast cancer. Our expectation is that successful completion of the proposed work will identify a specific biomarker for TNBC that could be targeted by novel therapeutic strategies. The proposed investigations will help in understanding the role of AnxA2 expression in the incidence of TNBC in various ethnic groups.