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Co-led the work that made pembrolizumab the first tumour-agnostic cancer drug approval, for mismatch-repair-deficient tumours.
Trained at Johns Hopkins with Vogelstein and Kinzler, where he co-founded Personal Genome Diagnostics and helped establish circulating tumour DNA as a clinical tool. The 2015 and 2017 studies of PD-1 blockade in dMMR tumours led to the 2017 tissue-agnostic approval of pembrolizumab. At MSK he co-led the dostarlimab rectal cancer programme.
| Title | Journal | Year |
|---|---|---|
| PD-1 blockade in tumors with mismatch-repair deficiency | New England Journal of Medicine | 2015 |
| Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade | Science | 2017 |
| Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency | New England Journal of Medicine | 2022 |
| KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer | New England Journal of Medicine | 2020 |
Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.
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.
The evidence that molecular cyst-fluid testing can spare operations, now part of specialist practice although not a universal standard.
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.
It reframed resistance as selection rather than mutation, which is why the field now asks how to suppress a pre-existing clone rather than how to prevent a new mutation, and why ctDNA is the natural monitoring tool.
A GNAS mutation in cyst fluid says the cyst is an IPMN, and in a cancer it says the cancer came from one, which is the molecular basis of cyst triage.
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 Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency, Dostarlimab, Mismatch-repair deficient (MSI-high) colorectal cancer, Memorial Sloan Kettering Cancer Center.
Shares Dostarlimab, Mismatch-repair deficient (MSI-high) colorectal cancer, Rectal cancer, Colorectal cancer.
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) colorectal cancer.
Shares Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency, Dostarlimab, Mismatch-repair deficient (MSI-high) colorectal cancer, Memorial Sloan Kettering Cancer Center.
Shares Mismatch-repair deficient (MSI-high) colorectal cancer, Rectal cancer, Pembrolizumab, Colorectal cancer.
Shares Dostarlimab, Mismatch-repair deficient (MSI-high) colorectal cancer, Rectal cancer, Immune checkpoint inhibitors.
Shares Dostarlimab, Mismatch-repair deficient (MSI-high) colorectal cancer, Rectal cancer, Immune checkpoint inhibitors.