Overcoming Challenges in KRAS Inhibitor Development: Organoid-Based Solutions for Targeting the ‘Undruggable’
- Patient-derived organoids (PDOs) are patient avatars able to mirror clinical response of patients
- PDOs exhibit variable sensitivity profiles to KRAS inhibitors, making them valuable tools for investigating both primary and acquired resistance mechanisms
- PDOs enable testing of combination treatments to overcome resistance—for example, KRAS G12C-mutant organoids resistant to Adagrasib show improved response with Afatinib cotreatment, unlike G12D-mutant counterparts