Single Cell Sampling of Signaling Activity in Triple Negative Breast Cancer

 描述（由申请人提供）：乳腺癌通常根据三种不同受体的存在/不存在分为四种亚型：管腔A、管腔B、HER 2和三阴性/基底样。三阴性乳腺癌（TNBC）影响大约15%的乳腺癌患者，并且比其他亚型的预后更差。与一般乳腺癌和特别是TNBC相关的主要挑战是患者之间和个体肿瘤内疾病的异质性。这阻碍了开发有效疗法的努力。正如其他人所指出的那样，“以单细胞分辨率描述肿瘤的能力将提高我们确定最佳治疗方案和预测疾病结果的能力”。拟议的多学科研究计划旨在开发和应用一种技术，在TNBC的单细胞水平上同时评估多种酶的细胞内信号传导活性。 我们将比较和对比2D和3D细胞培养条件以及拮抗剂和激动剂对信号传导活性的影响。此外，我们将评估表现出独特信号行为的亚群的存在。在单个细胞水平上逐个患者定义异质异常信号传导行为的能力可以解决被广泛认为是TNBC中最迫切的需求：缺乏管理三阴性疾病患者的指南。

 DESCRIPTION (provided by applicant): Breast cancer is commonly divided into four subtypes based on the presence/absence of three distinct receptors: Luminal A, luminal B, HER2, and triple negative/basal-like. Triple negative breast cancer (TNBC) affects approximately 15% of breast cancer patients and has a poorer prognosis than the other subtypes. A major challenge associated with breast cancer in general and TNBC in particular is the heterogeneity of the disease, both between patients and within individual tumors. This has hampered efforts to develop effective therapies. As pointed out by others "the ability to describe tumors at the resolution of single cells will enhance our ability to determine the best treatment options and to anticipate disease outcome". The proposed multidisciplinary research program seeks to develop and apply a technology that simultaneously assesses the intracellular signaling activity of multiple enzymes at the single cell level in TNBC. We'll compare and contrast the influence of 2D and 3D cell culture conditions as well as antagonists and agonists on signaling activity. In addition, we'll evaluate the presence of subpopulations exhibiting unique signaling behavior. The ability to define heterogeneous aberrant signaling behavior at the single cell level on a patient-by-patient basis could address what is widely viewed as the single most pressing need in TNBC: the absence of guidelines to manage patients with triple-negative disease.