Exploring BCL-XL addiction in pancreatic ductal adenocarcinoma

探索胰腺导管腺癌中的 BCL-XL 成瘾

• 批准号: 9263683
• 负责人: Ryan Soderquist
• 金额: $ 5.71万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263683
• 关键词: Address; Animal Model; Apoptosis; Apoptotic; BCL1 Oncogene; BCL2 gene; Biochemical; Biological Assay; Biological Markers; Cell Death; Cell Line; Cell Survival; Cell model; Clinical Research; Dependency; Development; Disease; Equilibrium; Event; Family; Genetic Screening; Genomic approach; Genomics; Growth; Hematologic Neoplasms; Human; In Vitro; KRAS2 gene; Lead; Light; Malignant Neoplasms; Mitochondria; Modeling; Mutation; Oncogenes; Pancreatic Ductal Adenocarcinoma; Pathway interactions; Patients; Pharmaceutical Preparations; Process; Protein Family; Proteins; Reporting; Research; Resistance; Series; Solid; Solid Neoplasm; Survival Rate; Technology; Testing; Therapeutic; Work; addiction; cancer cell; clinical efficacy; clinical translation; clinically relevant; design; improved; in vivo; inhibitor/antagonist; leukemia/lymphoma; loss of function; member; mimetics; neoplastic cell; novel drug combination; novel therapeutic intervention; pancreatic cancer cells; potential biomarker; preclinical efficacy; public health relevance; resistance mechanism; structural genomics; therapeutic target; tumor

 DESCRIPTION (provided by applicant): Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a low cure rate and few therapeutic options. We recently discovered that approximately 50% of the pancreatic cancer cell lines tested in our lab (14 out of 31 lines) are highly sensitive to the selective BCL-XL inhibitor WEHI-539. Therefore, we will evaluate the potential efficacy of BCL-XL as a therapeutic target in PDAC both in vitro and in vivo. In addition, we will identify potential biomarkers of BCL-XL addiction, characterize mechanisms of sensitivity and resistance, and uncover novel drug combinations to further potentiate the activity of BCL-XL inhibitors in PDAC.

 描述（由申请人提供）：胰腺导管腺癌（PDAC）是一种致命的疾病，治愈率低，治疗选择少。我们最近发现，在我们实验室测试的胰腺癌细胞系中，约有50%（31个细胞系中的14个）对选择性BCL-XL抑制剂WEHI-539高度敏感。因此，我们将在体外和体内评估BCL-XL作为PDAC治疗靶点的潜在功效。此外，我们将确定BCL-XL成瘾的潜在生物标志物，表征敏感性和耐药性的机制，并发现新的药物组合，以进一步增强BCL-XL抑制剂在PDAC中的活性。