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Cell Line Panel Profiling for Discovery of Multiple Myeloma Therapeutics

用于发现多发性骨髓瘤治疗方法的细胞系面板分析

基本信息

批准号：
8648609
负责人：
Peter Krutzik
金额：
$ 18.97万
依托单位：
PRIMITY, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-09 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8648609
关键词：
Accounting Address Antigens Antineoplastic Agents Biological Assay Cancer Patient Cell Count Cell Cycle Cell Line Cell Survival Cell model Cell surface Cells Cellular Stress Chemicals Chromosome abnormality DNA Damage Development Diagnosis Disease Disease Progression Exposure to Flow Cytometry Genetic Genetic Heterogeneity Genetic Variation Grant Growth Health Hour Human Resources Inhibitory Concentration 50 Label Libraries Literature Logistics Malignant Neoplasms Measures Medicine Mitochondria Modeling Multiple Myeloma Mutate Nature Oncogenes Patients Pattern Pharmaceutical Preparations Phase Population Process Recovery Resources Running Sampling Savings Small Business Innovation Research Grant Solutions Stress System Technology Testing Therapeutic Time Tube Variant base cancer therapy cell type chemotherapeutic agent cost drug discovery established cell line genetic profiling genetic variant improved in vitro Model novel patient population public health relevance research study response screening standard of care tool trend

项目摘要

Project Summary The genetic and transcriptional makeup of Multiple Myeloma is particularly heterogeneous, with several oncogenes routinely mutated and multiple chromosomal aberrations noted in different combinations. The heterogeneous nature of this disease makes it impossible to identify a single cellular model or "ideal" patient that could be utilized in a drug discovery campaign. To account for patient diversity in characterizing new anti-cancer drugs, a recent trend has been to test compounds on large panels of established cell lines in parallel. These panels provide the necessary genetic breadth and have been shown to be highly informative. However the utility of this powerful approach is limited due to the logistics and complications associated with running many cell line experiments in parallel. The increased number of cell lines multiplies the cost, manpower, and time required to perform these screens. This limits the types of assays that can be performed and also dramatically reduces the numbers of compounds that can be profiled, severely limiting the impact of this approach. In this Phase I SBIR proposal we outline a solution to these problems with the implementation of a novel cell-based assay platform that multiplexes experimental readouts with libraries of cell lines. The proposed assay platform exploits Primity's CellCode multiplexing technology which labels cell populations with unique fluorescent signatures such that multiple cell lines can be combined in a single tube and analyzed simultaneously. Using this technology, panels of up to 40 cell lines can be assayed with multiple end-points from a single sample, dramatically reducing the time and resources required - while simultaneously increasing the amount of information obtained from each cell line. Thus, the successful completion of these studies will establish a novel drug discovery tool for multiple myeloma that accounts for a wide variety of genetic diversity and maintains the throughput necessary for all phases of the drug discovery process.

项目总结