Joseph Combs
Seminars
Thursday 10th September 2026
Overcoming Challenges in KRAS Inhibitor Development (Organoid-Based Solutions for Targeting the ‘Undruggable’)
10:00 am
- Predicting which patients will respond and where resistance will emerge — screening 50+ organoids across G12C, G12D, G12V, and rarer G12/G13/Q61 alleles reveals response variability within a single mutation, enabling stratification ahead of Phase 1/2 trials;
- Building the case for combination therapy — models with intrinsic resistance to sotorasib and adagrasib show that adding the EGFR inhibitor afatinib restores response, offering patient-relevant platform to build your rationale for next-generation KRASi combinations;
- Mapping the mechanisms driving resistance at single-cell resolution — inducing persister and resistant organoid populations, then applying scRNA-seq, uncovers distinct clonal escape routes to guide new target and biomarker discovery .
