Role of MGMT as biomarker in colorectal cancer

作     者：Alessandro Inno Giuseppe Fanetti Maria Di Bartolomeo Stefania Gori Claudia Maggi Massimo Cirillo Roberto Iacovelli Federico Nichetti Antonia Martinetti Filippo de Braud Ilaria Bossi Filippo Pietrantonio 

作者机构：Medical Oncology Department Ospedale Sacro Cuore Don Calabria Negrar 37100 Verona Italy Radiotherapy Unit European Institute of Oncology 20100 Milan Italy Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori 20100 Milan Italy 

出 版 物：《World Journal of Clinical Cases》 (世界临床病例杂志)

年 卷 期：2014年第2卷第12期

页      面：835-839页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Colorectal cancer O6-methylguanine DNA methyltransferase Temozolomide Dacarbazine Biomarker 

摘      要：O6-methylguanine DNA methyltransferase(MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients.