Critical appraisal of MGMT in digestive NET treated with alkylating agents.

Endocrine-related Cancer
Louis de MestierJérôme Cros

Abstract

The efficacy of alkylating agents (temozolomide, dacarbazine, streptozotocin) in patients with advanced neuroendocrine tumors (NETs) has been well documented, especially in pancreatic NETs. Alkylating agents transfer methyl adducts on DNA bases. Among them, O6-methylguanine accounts for many of their cytotoxic effects and can be repaired by the O6-methylguanine-methyltransferase (MGMT). However, whether the tumor MGMT status could be a reliable biomarker of efficacy of alkylating agents in NETs is still a matter of debate. Herein, we sought to provide a critical appraisal of the role of the MGMT status in NETs. After reviewing the molecular mechanisms of repair of DNA damage induced by alkylating agents, we aimed to comprehensively review the methods of determination of the MGMT status and its impact on prognosis, prediction of objective response and progression-free survival in patients with advanced digestive NETs treated by alkylating agents. About half of pancreatic NETs are MGMT-deficient, as determined by impaired tumor MGMT expression or by MGMT promoter methylation. Overall, while published studies are heterogeneous and mostly limited in size, they advocate that MGMT deficiency may be a relevant biomarker for increased ...Continue Reading

Citations

Dec 29, 2020·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Antonio ViúdezAna De Jesús Acosta
Apr 13, 2021·Reviews in Endocrine & Metabolic Disorders·Paula Espinosa-OlarteRocio Garcia-Carbonero

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