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Test the tumour for a broken DNA spell-checker; if it has one, immunotherapy before surgery melts most tumours and in the rectum can replace surgery altogether.
This diagnostic-therapeutic pairing links universal testing for mismatch repair deficiency or microsatellite instability at diagnosis of colorectal cancer with neoadjuvant immune checkpoint blockade. dMMR tumours carry thousands of frameshift neoantigens and respond to checkpoint inhibitors far more than to chemotherapy, and a primary tumour left in place provides antigen for priming. In NICHE-2 a short course of nivolumab plus ipilimumab before colon surgery produced pathological complete responses in most patients, the MSK dostarlimab rectal cohort and AZUR-1 showed that rectal tumours can reach clinical complete response and avoid surgery, and the phase 3 ATOMIC trial showed a benefit from adjuvant atezolizumab. MMR testing is the gate that opens all of these options.
Shares ATOMIC (Alliance A021502), AZUR-1, NICHE-2, Dostarlimab.
Shares NICHE-2, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Ipilimumab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation.
Shares AZUR-1, Clinical complete response (cCR), Dostarlimab, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares AZUR-1, Dostarlimab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer.
Shares Ipilimumab, Nivolumab, Colorectal cancer, Immune checkpoint inhibitors.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Ipilimumab, Atezolizumab, Nivolumab.
Shares AZUR-1, Clinical complete response (cCR), Colorectal cancer.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Ipilimumab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Nivolumab.