title: Role of MGMT as biomarker in colorectal cancer.
abstract: O(6)-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.
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Inno
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanetti
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Maggi
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cirillo
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Nichetti
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Martinetti
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bossi
authors.affiliation: Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
keywords: Biomarker; Colorectal cancer; Dacarbazine; O6-methylguanine DNA methyltransferase; Temozolomide