A study published in Nature has identified a key epigenetic mechanism that drives resistance to 5-fluorouracil (5-FU) in colorectal cancer. Researchers found that increased activity of the enzyme EHMT2 leads to suppression of a tumor-suppressor gene called PPM1B, allowing cancer cells to survive chemotherapy and continue growing.
The study showed that EHMT2 modifies gene expression by adding epigenetic marks that silence PPM1B. This change helps cancer cells avoid cell death and become resistant to 5-FU treatment. Data from patient databases also confirmed that high EHMT2 levels and low PPM1B levels are linked to poorer treatment outcomes and survival.
Importantly, blocking EHMT2 using genetic methods or a drug inhibitor restored sensitivity to 5-FU in lab models, animal studies, and patient-derived organoids. Tumors treated with the combination therapy showed reduced growth without added toxicity, suggesting a potential new strategy to overcome chemotherapy resistance in colorectal cancer.