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Project 2: Identifying Metabolic vulnerabilities and targets in cancers with mutations in hamartoma genes

项目 2：识别错构瘤基因突变癌症的代谢脆弱性和目标

基本信息

批准号：
10221614
负责人：
DAVID J. KWIATKOWSKI
金额：
$ 54.42万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10221614
关键词：
ATP Synthesis Pathway Acetyl-CoA Carboxylase Apoptosis Ascorbic Acid Biguanides Biochemical Cancer cell line Carboplatin Categories Cell Line Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Combined Modality Therapy Data Defect Development Dissection Dose Drug Combinations Drug Targeting Enzymes FRAP1 gene Fatty Acids Funding Genes Genetic Genetic Predisposition to Disease Genetically Engineered Mouse Growth Hamartoma Homeostasis Human Immune Impairment In Vitro K-ras mouse model KRAS2 gene Laboratories MAP Kinase Gene Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Metabolic Metabolic Control Metabolism Modality Modeling Molecular Mus Mutation Non-Small-Cell Lung Carcinoma Normal Cell Oncogenes Oncology Oxidative Phosphorylation Oxygen PTEN gene Pancreas Pancreatic Ductal Adenocarcinoma Pathogenesis Pathway interactions Patients Pemetrexed Pharmaceutical Preparations Pharmacology Phenformin Play Pre-Clinical Model Principal Investigator Process Reporting Resistance Role STK11 gene Series Stress Syndrome TP53 gene TSC1 gene TSC2 gene Testing Therapeutic Tumor Burden Tumor Suppressor Genes Tumor Suppressor Proteins antitumor effect ascorbate base biomarker development biomarker-driven cancer cell cancer genetics docetaxel efficacy evaluation falls gain of function mutation in vivo inhibitor/antagonist loss of function mutation lung cancer cell metabolomics mutant novel patient population pre-clinical preclinical trial pressure programs rapid growth resistance mechanism response standard of care targeted agent tumor tumor metabolism

项目摘要

Program Director/Principal Investigator (Last, First, Middle):Kwiatkowski, David J. et al., Project 2: Cantley and Shaw Abstract Over the past five years it has become clear that many tumors rewire their metabolism to support rapid growth, but that the molecular details of how each tumor rewires its metabolism depends on the unique oncogenes and tumor suppressors that dominantly control metabolism, which include all of the hamartoma syndrome genes, as the PI3K/ mTOR/ LKB1 pathways play a major role in metabolic control in normal and cancer cells. The focus of this project is to better understand metabolic vulnerabilities and provide preclinical data that would support the development of biomarker driven clinical trials to evaluate such drugs in patients with germline or the many tumors containing sporadic mutations in hamartoma syndrome genes (PTEN, LKB1, TSC1, TSC2).

项目负责人/主要研究者（最后，第一，中间）：Kwiatkowski，大卫J.等人，项目2：Cantley & Shaw 摘要在过去的五年里，人们清楚地发现许多肿瘤会重新调整新陈代谢以支持快速生长，但是每个肿瘤如何重新连接其代谢的分子细节取决于独特的癌基因，主要控制代谢的肿瘤抑制因子，包括所有的错构瘤综合征基因， PI 3 K/ mTOR/LKB 1途径在正常和癌细胞的代谢控制中起主要作用。重点该项目的目的是更好地了解代谢的脆弱性，并提供临床前数据，开发生物标志物驱动的临床试验，以评估此类药物在生殖系或许多生殖系统疾病患者中的作用。错构瘤综合征基因（PTEN、LKB 1、TSC 1、TSC 2）中含有散发性突变的肿瘤。