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（由适用提供）：乳腺癌通常根据三个不同的接收器的存在/不存在分为四个亚型：腔A，Luminal B，HER2和三重阴性/基底样。三重阴性乳腺癌（TNBC）影响了大约15％的乳腺癌患者，并且预后较差。通常，与乳腺癌相关的主要挑战，尤其是TNBC是该疾病的异质性，无论是在患者和单个肿瘤内。这阻碍了开发有效疗法的努力。正如他人指出的那样：“在单个细胞的分辨率下描述肿瘤的能力将增强我们确定最佳治疗方案并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，该技术简单地评估了TNBC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。逐个患者在单个细胞水平上定义异构异常信号传导行为的能力可以解决TNBC中最紧迫的单一需求：缺乏管理三个为疾病的患者的指南。