Specific Targeting of MTAP-Deleted Tumors with a Combination of 2'-Fluoroadenine and 5'-Methylthioadenosine.

ABSTRACT: Homozygous deletion of the methylthioadenosine phosphorylase (MTAP) gene is a frequent event in a wide variety of human cancers and is a possible molecular target for therapy. One potential therapeutic strategy to target MTAP-deleted tumors involves combining toxic purine analogues such as 6'-thioguanine (6TG) or 2'-fluoroadenine (2FA) with the MTAP substrate 5'-deoxy-5'-methylthioadenosine (MTA). The rationale is that excess MTA will protect normal MTAP⁺ cells from purine analogue toxicity because MTAP catalyzes the conversion of MTA to adenine, which then inhibits the conversion of purine base analogues into nucleotides. However, in MTAP^- tumor cells, no protection takes place because adenine is not formed. Here, we examine the effects of

SUBMITTER: Tang B 

PROVIDER: S-EPMC6072572 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature