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NIHNATIONAL CANCER INSTITUTER01

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

Completed
Institution
Coriell Institute for Medical Research, NJ
Principal investigator
Xiaoxin Luke Chen
Funding
$618K
Duration
2020–2025
Open portfolio

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Abstract

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.

Research team

  • Xiaoxin Luke ChenPI
  • Michael Benjamin MajorPI

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R01NATIONAL CANCER INSTITUTEDevelopmental Therapeutics Study Section[DT]cooperativelytargeted therapypharmacological approachesproposal designedapproaches understandproven effectivehyperactivationkinases

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