权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A Prostate Cancer Dependency Map to Identify Tumor Subtype-Specific Vulnerabilities

用于识别肿瘤亚型特异性漏洞的前列腺癌依赖性图

基本信息

批准号：
10578640
负责人：
PETER S NELSON
金额：
$ 24.68万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10578640
关键词：
Address Androgen Receptor Behavior Benign Biological Cancer Biology Cancer cell line Carcinoma Cell Line Cells Characteristics Classification Clinical Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Communities DNA Sequence Alteration Data Data Set Defect Dependence Development Disease Distant Drug Screening ETS Family Gene Encyclopedias Exclusion Exhibits Foundations Genes Genetic Genetic Screening Genomic Instability Genomics Genotype Growth Homeostasis Human In Vitro International Knowledge Libraries Malignant Neoplasms Malignant neoplasm of prostate Maps Metastatic Prostate Cancer Modeling Molecular Morbidity - disease rate Mutation Neoplasm Metastasis Normal tissue morphology Oncogenes Organ Outcome Output Pathway interactions Patients Pharmaceutical Preparations Phenotype Recurrence Reiterated Genes Research Resistance Series Site Solid Neoplasm Technology The Cancer Genome Atlas Therapeutic Tissues Tumor Subtype United States Food and Drug Administration Work advanced prostate cancer cancer genome cancer subtypes cancer type cell type design drug sensitivity epigenomics experimental study functional loss genome-wide genomic data improved outcome in vivo in vivo evaluation insight loss of function molecular subtypes mortality neoplastic cell new technology novel novel anticancer drug novel therapeutics patient derived xenograft model personalized approach pharmacologic precision medicine prostate cancer cell line prostate cancer metastasis prostate cancer model public repository response small hairpin RNA therapeutic target tool tumor tumor growth tumor heterogeneity tumor progression tumorigenesis

项目摘要

PROJECT SUMMARY/ABSTRACT Despite the advances in our knowledge of cancer biology and the approval of new cancer drugs by the Food and Drug Administration (FDA), very few patients with solid tumors that have spread to distant sites (metastases) are cured of their disease. This is true of metastatic prostate cancer (mPC). Consequently, substantial research is directed toward identifying new targets and treatments. New technologies which we and others have developed, now provide unprecedented approaches for deeply characterizing tumors on a comprehensive scale. Studies using these approaches have determined that mPC is comprised of multiple distinct subtypes – a subset of these are defined by specific genomic alterations in oncogenes and genes that normally function to suppress tumor growth. Others are defined by the phenotype – characteristics that influence function and behavior. Notably, a number of these subtypes are now known to have different vulnerabilities to particular therapies – knowledge that underlies a more precision approach for treatment. However, for most subtypes we do not currently have knowledge of their particular vulnerabilities nor do we have therapeutics that can halt their growth/progression. Powerful high-throughput approaches to dissect the function of every gene in a particular cancer genome have been deployed to construct cancer dependency maps (DEPMAP) in many cancer types. These approaches are highly ‘discovery driven’ as they approach the problem of identifying cancer vulnerabilities in a systematic rather than hypothesis-driven fashion. However, prostate cancer is largely excluded from these International projects due to the very limited number of mPC models available to conduct these large scale experiments. In this proposal, we aim to identify new treatment avenues for advanced lethal prostate cancer. We will use multiple new models of metastatic prostate cancer that we have developed and characterized to identify PC subtype specific dependencies using genome-wide loss-of-function screens. In parallel, we will evaluate growth inhibitory effects of drug libraries of approved agents as well as compounds in development. Combinations of agents that exploit genomic dependencies will be tested in vivo against a panel of patient derived xenograft (PDX) lines with and without the predicted vulnerability.

项目总结/文摘