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Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.
MSS CRC has few neoantigens, TGF-beta-rich stroma, and liver metastases that induce systemic tolerance. Approaches: botensilimab + balstilimab (Fc-enhanced anti-CTLA-4; 17% ORR in the phase 1, 21% in the later cohort selected for the absence of liver metastases), KRAS G12C inhibitor + PD-1, anti-EGFR + PD-1 in RAS wild-type (AVETUX), radiation to liver metastases, CEA-directed T-cell engagers.
The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.
One of the most cited reviews Europe PMC returns for CTLA-4 in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.
This study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.
Shares CheckMate 8HW, KEYNOTE-177, Hot vs cold tumours, CTLA-4.
Shares CheckMate 8HW, KEYNOTE-177, CTLA-4, 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 CheckMate 8HW, CTLA-4, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), 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 Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Cold tumours and the immunosuppressive microenvironment, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares CheckMate 8HW, KEYNOTE-177, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial, CheckMate 8HW, CTLA-4, PD-1.
Shares Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial, CheckMate 8HW, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Hot vs cold tumours.
Shares CodeBreaK 300, KRAS & RAS inhibitors, KRAS, Colorectal cancer.