A study has identified a key molecular pathway that helps explain why colon cancer becomes resistant to chemotherapy.
Researchers found that a protein called SALL4 is highly active in colon cancer and is linked to more advanced disease and poorer survival. SALL4 turns on another gene called CRIPTO, which is normally inactive in adults but reappears in aggressive cancers. Together, they increase cancer stem cells, which can repair chemotherapy damage and survive treatment.
The study also shows that this SALL4–CRIPTO system activates the JAK-STAT signaling pathway, helping cancer cells maintain their stem-like, drug-resistant state. When scientists blocked this pathway using a drug called ruxolitinib, cancer cells became more sensitive to chemotherapy again.
These findings suggest that SALL4 and CRIPTO could be used as biomarkers to predict treatment response and may also serve as new targets for overcoming chemotherapy resistance in colon cancer.