Title |
Promoter CpG Island Hypermethylation of the DNA Repair Enzyme MGMT Predicts Clinical Response to Dacarbazine in a Phase II Study for Metastatic Colorectal Cancer
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Published in |
Clinical Cancer Research, April 2013
|
DOI | 10.1158/1078-0432.ccr-12-3518 |
Pubmed ID | |
Authors |
Alessio Amatu, Andrea Sartore-Bianchi, Catia Moutinho, Alessandro Belotti, Katia Bencardino, Giuseppe Chirico, Andrea Cassingena, Francesca Rusconi, Anna Esposito, Michele Nichelatti, Manel Esteller, Salvatore Siena |
Abstract |
O(6)-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O(6)-guanine in DNA. Approximately 40% of colorectal cancers (CRC) display MGMT deficiency due to the promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O(6)-guanine site, inducing base pair mismatch; therefore, activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild-type). |
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