Research suggests that the removal of uracil by uracil DNA glycosylase may limit the effectiveness of the drug pemetrexed, but this limitation can be overcome with methoxyamine, which inhibits base excision repair. The relationship between uracil DNA glycosylase and pemetrexed cytotoxicity is being studied in various types of cancer cells, including non-small cell lung cancer and bladder cancer. The mechanisms of pemetrexed cytotoxicity and genome instability are complex and involve multiple cellular processes, including base excision repair and folate stress.