A study in Nature reports a new mechanism behind liver metastasis in colorectal cancer. Researchers found that Enolase 2 (ENO2) acts beyond metabolism, helping tumors evade immune detection.
ENO2 binds to macrophage migration inhibitory factor (MIF), protecting it from degradation and enabling its release. This signals immune cells to become immunosuppressive, creating a tumor-friendly environment in the liver and weakening anti-tumor responses. High ENO2 levels were linked to greater metastasis and poorer survival.
The team identified pyrithioxin, an older neuroprotective drug, as a potential inhibitor of this pathway. In mouse models, blocking ENO2 reduced liver metastases by more than half.
These findings are particularly relevant for microsatellite stable colorectal cancer, which often resists immunotherapy, and suggest a new strategy to make tumors more responsive to treatment.