Inhibition of DNA methylation by antisense oligonucleotide MG98 as cancer therapy.
Results of preclinical studies and clinical phase I/II trials suggest that the antisense oligodeoxynucleotide and DNA methyltransferase inhibitor MG98 can safely and effectively lead to reactivation of methylation silence tumor suppressor genes. It is possible that daily or continuous dosing of MG98 might be more active and less toxic than intermittent dosing. Combination of MG98 with other agents having completely different mechanisms of action seems reasonable. One clinical trial now under way is evaluating the use of MG98 in combination with interferon-alpha in patients with advanced renal cell carcinoma (RCC). Because of the current preclinical and clinical evidence, further trials of MG98 as therapy for RCC would be of interest.
Amato
Robert J
RJ
Genitourinary Oncology Program, The Methodist Hospital Research Institute, Houston, TX 77030, USA. ramato@tmh.tmc.edu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D013873:Thionucleotides / Q000627:therapeutic use*
C483603:MG 98 phosphorothioate antisense oligodeoxynucleotide; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases