Chemical Reprogramming of FBXW7 Cancer Mutations

FBXW7 is a tumor suppressor that maintains normal cellular function by promoting the degradation of proteins that drive cancer progression. In many human cancers, particularly endometrial and colorectal cancers, FBXW7 is inactivated by recurrent mutations that disrupt its ability to recognize and degrade oncogenic substrates. Dr. Zhang and his team aim to develop chemical strategies to address these cancer-associated mutations. They will explore approaches to reprogram mutant FBXW7 to promote targeted degradation of disease-relevant proteins and to restore its native tumor-suppressive function and downstream signaling control. Successful completion of this work will provide new chemical tools for understanding and manipulating mutant FBXW7. It will also establish a foundation for therapeutic strategies that harness or restore the function of mutated tumor suppressors in cancer.