Organoids cultured from patient-derived colorectal cancer cells have been used to demonstrate for the first time that tumors which have developed resistance to the full range of existing treatments, across chemotherapies, targeted therapies and immunotherapies, retain a requirement for Werner helicase (WRN) for survival. WRN has a key role in the maintenance of genome stability, but although loss of WRN is known to initiate synthetic lethality in DNA mismatch repair deficient colorectal cancer, studies into the effect of inhibiting that helicase have to date been limited to a handful of cell lines.