Epigenetic DNA modifications, like methylation, heritably alter gene expression without changing the genetic code. Aberrant epigenetic alterations and dysregulated methylation often drive cancer development. Identifying such alterations could lead to new cancer biomarkers or treatment targets. Colorectal cancer in particular could benefit from epigenetic biomarkers, as it is the third deadliest cancer globally and has limited early detection methods. In a recent study, researchers screened methylation databases of colorectal cancer patients, and they honed in on HAND2, a transcription factor whose promotor region was frequently methylated in these patients. In the lab, experiments demethylating HAND2 reverted its expression in cultured colorectal cancer cells. Demethylation of HAND2 inhibited pro-cancer behavior — proliferation, invasion, and migration — in these cells. HAND2 demethylation also suppressed tumor growth relative to controls in tumor xenograft experiments. Further tests determined that demethylated HAND2 could bind the ERK protein, a member of a key growth signaling pathway, and reduce its activation. While more research is needed, these results suggest that HAND2 methylation is an important pro-cancer event in colorectal cancer. This makes HAND2 methylation a potential early biomarker for colorectal cancer, which could lead to improved outcomes for patients.