DNMT1 and colorectal cancer: Hypoxia has been shown to downregulate the expression of DNMT1, DNMT3A and DNMT3B in human colorectal cancer cells.217 On the contrary, hypoxia results in HIF-dependent transcriptional activation of TET1.219, 220 Given that a hypoxic tumor microenvironment promotes DNA hypomethylation, efficacy of DNA demethylation agents, such as modulators of DNMTs/TETs, are likely suppressed in solid tumors as compared to hematological malignancies.