TAS::75 0849::TAS SBIR TOPIC 292 PHASE I DEVELOPMENT OF MOLECULAR PHARMACODYNAMI

TAS::75 0849::TAS SBIR 主题 292 分子药效的第一阶段开发

基本信息

批准号：
8338991
负责人：
DAVID CHIMENTO
金额：
$ 14.99万
依托单位：
ROCKLAND IMMUNOCHEMICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2012-06-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8338991
关键词：
Adenocarcinoma Cell Antibodies Antigens Antineoplastic Agents Apoptotic Baculovirus Expression System Biological Assay Breast Carcinoma Cancer cell line Cell Line Cell Proliferation Cell Survival Cells Clinical Clinical Trials Detection Development Disease Drug resistance Drug usage Enzyme-Linked Immunosorbent Assay HCT116 Cells HT29 Cells Human Immunoassay Ligands MDA MB 231 Malignant Epithelial Cell Malignant Neoplasms Manuals Measures Molecular Monitor Neoplasm Metastasis Outcome Papillary adenocarcinoma Pathway interactions Pharmaceutical Preparations Phase Phosphorylation Production Proteins Protocols documentation Reagent Recombinant Antibody Recombinant Fusion Proteins Recombinant Proteins Research Personnel Sampling Signal Pathway Signal Transduction Small Business Innovation Research Grant Testing Treatment Efficacy Validation Writing base cancer cell cancer therapy cell growth colon cancer cell line malignant stomach neoplasm meetings migration mutant protein activation prototype

项目摘要

The RON and c-MET signal pathways are critical regulators of cell growth, survival, migration, differentiation, and drug resistance. High levels of activated RON or c-MET have been observed in a number of human cancers. Activation of RON and c-MET by phosphorylation initiates a signal transduction cascade that promotes cancer cell proliferation, invasiveness, apoptotic and drug resistance, and metastasis. A number of anticancer drugs currently in clinical trials are targeting both of of these pathways. Further, the activation state and protein levels of RON and c-MET are good indicators of drug treatment efficacy and cancer cell survival outcome. In Phase I, we will develop a quantitative immunoassay to monitor the phosphorylation state of either RON or GAB1 (the target of c-MET) in various activated and unactivated cancer cell lines. The ELISA kit will be manufactured and written SOPs created. In Phase II, we will use the RON or GAB1 kit to measure activation and protein levels in clinical samples from a wide range of cancers and additional PD assays, including studies using drugs that upregulate or downregulate these targets. The availability of RON and GAB1 detection kits will aid clinicians and researchers to monitor these proteins in a number of diseases and predict the efficacy of cancer treatment.

RON和C-MET信号途径是细胞生长，生存，迁移，分化和耐药性的关键调节剂。在许多人类癌症中已经观察到了高水平的活化的RON或C-MET。通过磷酸化激活RON和C-MET会启动信号转导级联反应，该级联反应促进癌细胞增殖，侵入性，凋亡和耐药性以及转移。目前正在临床试验中的许多抗癌药针对这两种途径。此外，RON和C-MET的激活状态和蛋白质水平是药物治疗功效和癌细胞存活结果的良好指标。在第一阶段，我们将开发一种定量免疫测定法，以监测各种激活和未激活的癌细胞系中RON或GAB1（C-MET的靶标）的磷酸化态。 ELISA套件将是制造和书面SOP的。在第二阶段，我们将使用RON或GAB1试剂盒来测量来自广泛癌症的临床样品中的激活和蛋白质水平，以及其他PD分析，包括使用上调或下调这些靶标的药物的研究。 RON和GAB1检测试剂盒的可用性将有助于临床医生和研究人员在多种疾病中监测这些蛋白质，并预测癌症治疗的功效。