The present invention provides isolated nucleic acids encoding delta DNA methyltransferase 3B molecules that are involved in the treatment and prevention of cancers such as, but not limited to, lung cancer. The delta DNA methyltransferase 3B molecules of the present invention are found to play a critical role in promoter-specific methylation of tumor suppressor genes. The DNA methyltransferase 3B molecules of the present invention are provided as therapeutic targets for identifying inhibitors of DNA methyltransferase. Such inhibitors are contemplated for the treatment and/or prevention of cancers. In particular embodiments, the present invention involves the treatment and prevention of a non-small cell lung cancer.