Programmed cell death 1 (PD-1) immunotherapy (pembrolizumab, nivolumab) has become the standard in patients with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) tumors, conferring durable responses, and current research is exploring bimodal synergies (ICI and anti VEGF/EGFR, radiotherapy, or microbiota manipulation) for refractory microsatellite stable (MSS) tumors. This evidence concerns the gene VEGFA and mismatch repair cancer syndrome 1.