MGMT-activated DUB3 stabilises Nrf2/NCOA4 to modulate apoptosis and ferroptosis, driving temozolomide resistance in pancreatic neuroendocrine tumours (ENETS 2025) - Mar 5, 2025 - Abstract #F08; Location: Foyer; "INTRODUCTION O6-methylguanine DNA methyltransferase (MGMT) is a key DNA repair enzyme that removes methyl groups from O(6)-alkylguanine in DNA, introduced by temozolomide (TMZ). CONCLUSION MGMT upregulation confers TMZ resistance in PanNETs by inhibiting apoptosis and enhancing ferroptosis sensitivity through DUB3-mediated Nrf2 and NCOA4 stabilisation. Targeting ferroptosis, particularly with agents like Erastin, may offer a strategy to overcome MGMT-associated TMZ resistance."
Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • MGMT • NCOA4 • SLC7A11
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Cheng Z1; Yu F H1; Chen R A1; Wang Y Y1; Chen X Y1; Tan H Y2
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