Overview
- Using the CANDiT machine-learning framework, researchers scanned more than 4,600 tumors to find network targets capable of restoring the differentiation gene CDX2.
- The approach pinpointed PRKAB1, and treatment with the investigational agonist PF-06409577 restored CDX2 in colorectal cancer stem cells that then underwent self-destruction.
- Efficacy was demonstrated in patient-derived organoids at UC San Diego’s HUMANOID Center, supporting human-relevant preclinical validation.
- A 50-gene response signature identified likely beneficiaries, with computer-simulated trials across over 2,100 patients suggesting up to a 50% reduction in recurrence and death that requires prospective clinical testing.
- PF-06409577 has Phase I safety data but no proven clinical efficacy, and the team is optimizing compounds, expanding CANDiT to other solid tumors, and investigating why reprogrammed cancer stem cells die.