Colon cancer cells better suppressed by protein degradation
A new type of cancer drug that fully degrades a protein rather than merely blocking it proves significantly more effective against colorectal cancer cells in laboratory research. Researchers report this in eLife.
In most colorectal cancers, a specific signalling system is overactive: the WNT/beta-catenin system. This system drives cells to keep dividing. Existing drugs that target this system have shown limited effectiveness, despite the approach appearing promising in theory. Researchers have now found out why. The study shows that existing drugs switch off a protein called tankyrase but do not remove it. That has unexpected consequences.
Accumulation as the problem
When tankyrase is switched off but not destroyed, it builds up inside the cell. This matters because the protein then acts as a scaffold that holds other proteins in place. This disrupts the mechanism by which the cell should break down beta-catenin. Paradoxically, the drug makes the problem worse through a separate effect.
Full degradation works better
The researchers developed a so-called PROTAC: a molecule that does not block tankyrase but instead guides the protein to the cell's own waste-disposal machinery. In cultured colorectal cancer cells, this suppressed the WNT/beta-catenin system more strongly than the existing drug did. The research was conducted in cultured cells in the laboratory, not in humans or animals.
Search terms to explore further: WNT beta-catenin signaling cancer, PROTAC protein degradation therapy, tankyrase colorectal cancer