Jean-Charles Soria, SVP and Oncology Therapeutic Area Head at Amgen, shared on LinkedIn:
“Mismatch Repair Deficiency: From DNA repair failure to immunotherapy sensitivity
- Loss of MMR → microsatellite instability → hypermutation → abundant neoantigens
- Immune context: TIL-rich & inflamed, but immune checkpoints (PD-1, CTLA4, LAG3) and fibrotic stroma enable escape
- Therapy: PD-1 ± CTLA4 blockade effective across cancers, but 25–40% show primary or acquired resistance
- Future: neoadjuvant ICBs, WRN helicase inhibitors (synthetic lethality), frameshift peptide vaccines, aspirin prevention in Lynch?”
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