This CRUK-funded study, led by the CRUK Scotland Centre and co-authored by researchers in the CRUK Oxford Centre as part of the CRC-STARS initiative, uncovers a critical mechanism behind this therapeutic resistance.
The team found that when MAPK-targeting therapies are used in CRC treatment, CRC cells quickly adapt by activating a different pathway called Wnt signaling. This enables the CRC cells to become more stem-cell–like, which helps them survive the treatment.
However, the team also found that when the cells are less able to change their state, such as in early metastatic disease or in tumours with specific mutations, MAPK-targeted therapies produce strong responses.
Their work highlights that strategies to restrict cell-state transitions or exploit windows of vulnerability in early metastasis could improve the effectiveness of MAPK-targeted treatments for CRC.
Read the full paper in Nature.
CRC-STARS brings together over 40 research experts from across the UK, Spain, Italy and Belgium to find kinder, better treatments for CRC. Read more about the initiative, which is co-led by Professor Simon Leedham from the Nuffield Department of Medicine at the University of Oxford.