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First author of the studies that showed mismatch-repair-deficient tumours respond to PD-1 blockade regardless of origin.
Dung T. Le is Professor of Oncology and Co-Director of GI Cancer Immunotherapy at Johns Hopkins Hospital and the Sidney Kimmel Comprehensive Cancer Center. She is known as first author of the studies showing that mismatch-repair-deficient tumours respond to PD-1 blockade regardless of where they arise, leading the KEYNOTE-016 study and its extension that established pembrolizumab's tissue-agnostic activity. Her selected paper reports PD-1 blockade in tumours with mismatch-repair deficiency. She also works on GVAX and pancreatic cancer vaccines in colorectal and pancreatic cancer.
| Title | Journal | Year |
|---|---|---|
| PD-1 blockade in tumors with mismatch-repair deficiency | New England Journal of Medicine | 2015 |
| KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer | New England Journal of Medicine | 2020 |
| Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval | Science | 2017 |
Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.
Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).
This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.
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.
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma.
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, PD-1.
Shares KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer, PD-1, Pembrolizumab.
Shares KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ.
Shares KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, PD-1, Pembrolizumab.
Shares KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, 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, PD-1, Pembrolizumab.
Shares KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ.
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, 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, PD-1.