Single Cell Sampling of Signaling Activity in Triple Negative Breast Cancer

三阴性乳腺癌信号活动的单细胞采样

基本信息

批准号：
9045488
负责人：
DAVID S. LAWRENCE
金额：
$ 46.62万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-02 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9045488
关键词：
Address Affect Age Agonist Behavior Biochemical Biochemistry Biology Biomedical Engineering Breast Cancer Patient Breast Cancer cell line Cell Line Cells Chemicals Clinical Communities Cytometry Development Disease Disease Outcome Disease model Drug effect disorder ERBB2 gene Enzymes Epidermal Growth Factor Receptor Exhibits Exposure to Family Fluorescent Probes Functional disorder Future Guidelines Heterogeneity Individual Interdisciplinary Study Laboratories Light Measures Membrane Mole the mammal Monitor Oncologist Patient Selection Patients Pattern Pharmaceutical Preparations Phosphotransferases Protein Dephosphorylation Protein Kinase Protein Kinase Inhibitors Protein Tyrosine Kinase Protein phosphatase Reporter Research Resolution Role Sampling Signal Pathway Signal Transduction Surgeon Technology Tissues Tyrosine Kinase Inhibitor anticancer research base cancer heterogeneity clinical application design disease heterogeneity drug discovery effective therapy individual patient inhibitor/antagonist kinase inhibitor malignant breast neoplasm molecular subtypes new technology outcome forecast pre-clinical precision medicine programs protein kinase inhibitor public health relevance receptor response therapeutic effectiveness three dimensional cell culture triple-negative invasive breast carcinoma tumor tumor heterogeneity

项目摘要

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.

描述（由申请人提供）：根据是否存在三种不同的受体，乳腺癌通常分为四种亚型：Luminal A、Luminal B、HER2 和三阴性/基底细胞样乳腺癌 (TNBC)。大约 15% 的乳腺癌患者患有这种疾病，并且与其他亚型相比，其预后较差。与一般乳腺癌（特别是 TNBC）相关的一个主要挑战是该疾病之间的异质性。正如其他人指出的那样，“以单细胞分辨率描述肿瘤的能力将增强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，同时评估 TNBC 中单细胞水平上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传导行为的亚群的存在，以定义异质异常信号传导行为。基于每个患者的单细胞水平可以解决被广泛认为是 TNBC 最迫切的需求：缺乏管理三阴性疾病患者的指南。