Study links low BEX2 to colorectal cancer stem-like cells and higher relapse risk

A protein called BEX2 may help restrain “stem-like” behavior in colorectal cancer cells, a trait associated with treatment resistance and relapse, according to research highlighted by Medical News Today.

The report describes findings suggesting that tumors with lower BEX2 levels tend to show more aggressive features and are linked to poorer disease-free survival. In laboratory and animal studies, BEX2 appeared to limit cancer cells’ ability to self-renew, spread, and survive treatment.

How BEX2 may affect tumor behavior Researchers propose that BEX2 promotes the degradation of MCL1, a molecule that supports cancer cell survival and is often overexpressed in colorectal cancer. By helping break down MCL1, BEX2 may reduce activity in the Hedgehog signaling pathway.

Hedgehog signaling is described as a driver of cancer stem cell activity and is associated with treatment resistance and recurrence. When BEX2 is low or absent, MCL1 becomes more stable, which may activate Hedgehog signaling and enhance stem-like traits.

Potential therapeutic strategy The study suggests that targeting this BEX2–MCL1–Hedgehog axis could be a possible approach to reduce relapse risk. Strategies discussed include restoring BEX2 function or inhibiting MCL1 or Hedgehog signaling to help eliminate treatment-resistant, stem-like cancer cells.

Evidence and next steps The findings are supported by analyses of patient datasets, cell and laboratory experiments, and mouse models. Across these analyses, lower BEX2 levels were observed in colorectal cancer tissue compared with normal tissue and were associated with poorer outcomes.

The report notes that further research is still needed to validate BEX2 as a clinical biomarker or a therapeutic target.