High Throughput Screening of Agents in Bladder Cancer Cell Lines

膀胱癌细胞系中药物的高通量筛选

• 批准号: 8763785
• 负责人: Piyush Agarwal
• 金额: $ 1.06万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763785
• 关键词: Accounting; Address; Bladder; Bladder Neoplasm; CCR; Calmette-Guerin Bacillus; Cancer cell line; Cell Line; Cessation of life; Cisplatin; Clinical; Collaborations; Databases; Diagnosis; Disease; Epidermal Growth Factor Receptor; Epithelial; Explosion; Funding; Health; Lead; Life; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Mesenchymal; Muscle; Operative Surgical Procedures; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacotherapy; Prevalence; Recurrent disease; Refractory; Renal carcinoma; Research; Research Personnel; Resistance; Therapeutic; Treatment Efficacy; United States; Urologic Cancer; Urologic Oncology; Woman; base; burden of illness; cancer therapy; chemotherapy; high throughput screening; men; novel; prevent; standard of care; tumor

I have chosen two cell lines that represent the spectrum of bladder cancer cell lines: UMUC-3 and RT4. The former is a mesenchymal, high-grade, and a luminal tumor. The latter is an epithelial, low-grade, and a basal tumor. In summary, these cell lines represent some of the most difficult bladder tumors to treat but have unique features along the EMT spectrum and sensitivity to EGFR-based therapy that will help identify subtle differences among therapeutics. However, since they are relatively resistant to cisplatinum-based chemotherapy, they will hopefully identify new targets for bladder tumors refractory to standard of care therapy. Furthermore, these cell lines have been well-characterized in the literature and have sequenced in publically available cancer cell line databases. Using the platform established by Lou Stadt's group, we will screen 2000+ drugs against these cell lines to identify a novel agent. We will then explore in detail therapeutics identified by this strategy.

我选择了两种代表膀胱癌细胞系的细胞系：UMUC-3和RT4。前者是间充质，高级和腔肿瘤。后者是上皮，低度和基底肿瘤。总而言之，这些细胞系代表了一些最困难的膀胱肿瘤，但在EMT谱系中具有独特的特征和对基于EGFR的疗法的敏感性，这将有助于确定治疗剂之间的细微差异。但是，由于它们对基于顺铂的化学疗法相对抗性，因此有望确定膀胱肿瘤对护理疗法标准疗法难治性的新靶标。此外，这些细胞系在文献中已经很好地表征，并在公开可用的癌细胞系数据库中进行了测序。使用Lou Stadt组建立的平台，我们将针对这些细胞系进行筛选2000多种药物，以识别一种新型药物。然后，我们将详细探讨该策略确定的治疗剂。