Mechanisms and Targeted Therapy of NRF2-high Esophageal Squamous Cell Carcinoma

NRF2高食管鳞癌的机制及靶向治疗

• 批准号: 10851493
• 负责人: XIAOXIN Luke CHEN
• 金额: $ 8.12万
• 依托单位: CORIELL INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10851493
• 关键词: Mechanisms; Targeted; Therapy; NRF2; Esophageal

PROJECT SUMMARY This multiple-PI R01 proposal is designed to incorporate genetic and pharmacological approaches to understand the mechanisms of NRF2 hyperactivation in ESCC and to develop targeted therapy for Nrf2high ESCC. We believe Nrf2 and kinases are functionally interrelated, and thus cooperatively contribute to ESCC. In this proposal, we aim to characterize the molecular and phenotypic consequences of NRF2 hyperactivation in ESCC, determine the mechanisms of action and efficacy of NRF2 small molecule inhibitors in ESCC, and identify NRF2-responsive kinases and their functions in NRF2-driven ESCC biology. Through three independent yet tightly related Specific Aims, we will provide novel insights into pathway regulation and novel therapeutic targets/agents for NRF2high ESCC. If proven effective, some compounds may be further translated into the clinic for targeted therapy of NRF2high ESCC in the future.

项目摘要 该多重PI R01提案旨在结合遗传和药理方法 了解ESCC中NRF2过度激活的机制，并开发针对NRF2High的靶向疗法 ESCC。我们认为NRF2和激酶在功能上相互关联，因此有助于ESCC。 在此提案中，我们旨在表征NRF2过度激活的分子和表型后果 在ESCC中，确定NRF2小分子抑制剂在ESCC和 识别NRF2响应性激酶及其在NRF2驱动的ESCC生物学中的功能。通过三个 独立但密切相关的特定目的，我们将对途径调节和新颖的新见解 NRF2High ESCC的治疗靶标/剂。如果证明有效，可能会进一步翻译一些化合物 将来进入NRF2High ESCC靶向治疗的诊所。