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PI R 01提案旨在将遗传学和药理学方法结合起来， 了解ESCC中NRF 2过度激活的机制，并开发针对NRF 2高的靶向治疗 ESCC。我们认为Nrf 2和激酶在功能上是相互关联的，因此合作促进ESCC。 在这个建议中，我们的目标是表征NRF 2超活化的分子和表型后果 在ESCC中，确定NRF 2小分子抑制剂在ESCC中的作用机制和疗效，以及 鉴定NRF 2应答激酶及其在NRF 2驱动ESCC生物学中的功能。通过三 独立但密切相关的具体目标，我们将提供新的见解，途径调控和新的 NRF 2高ESCC的治疗靶点/药物。如果证明有效，一些化合物可能会进一步转化为 为临床应用于靶向治疗高NRF 2的食管鳞癌奠定了基础。