MGMT-activated DUB3 stabilises Nrf2/NCOA4 to modulate apoptosis and ferroptosis, driving temozolomide resistance in pancreatic neuroendocrine tumours

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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). Clinical studies in pancreatic neuroendocrine tumours (PanNETs) have confirmed its role in TMZ efficacy.

Aim(s): To investigate the regulatory mechanisms by which elevated MGMT expression in PanNETs reduces TMZ efficacy and to develop strategies to counteract this resistance.

Materials and methods: MGMT knockout and overexpression models were used in vitro and in vivo to examine MGMT's role in TMZ efficacy, with a focus on elucidating the molecular mechanisms of MGMT-mediated resistance via apoptosis and ferroptosis pathways.

Conference:

Presenting Author: Cheng Z

Authors: Cheng Z, Yu F, Chen R, Wang Y, Chen X,

Keywords: pancreatic neuroendocrine tumour, MGMT, temozolomide, ferroptosis,