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Co-discovered APC, the gatekeeper gene of colorectal cancer, and co-led the first cancer genome sequences.
Kenneth W. Kinzler is Professor of Oncology and Co-Director of the Ludwig Center at Johns Hopkins Hospital and the Sidney Kimmel Comprehensive Cancer Center. He is known for co-discovering APC, the gatekeeper gene of colorectal cancer, and for co-leading the first cancer genome sequences with his long-time partner Bert Vogelstein. His selected paper reports the identification of familial adenomatous polyposis locus genes from chromosome 5q21. He also developed the digital PCR and Safe-SeqS methods behind liquid biopsy, and continues to work on APC and Wnt signalling and genome sequencing.
| Title | Journal | Year |
|---|---|---|
| Identification of FAP locus genes from chromosome 5q21 | Science | 1991 |
| Cancer genome landscapes: about 140 driver genes, and each tumour needs only a handful | Science | 2013 |
| DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms | Science | 2020 |
| DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer | New England Journal of Medicine | 2022 |
For stage II colon cancer, where most patients are cured by surgery alone, a blood test can identify the minority who benefit from chemotherapy and spare everyone else its side effects. It does not yet prove that treating ctDNA-positive patients improves survival compared with not treating them.
A blood test can find early, treatable cancers in people who feel well, including cancers for which no screening exists. It is not a replacement for mammography or colonoscopy but a possible addition. Larger randomised trials are needed to show benefit outweighs harm.
The proof of principle for multi-cancer blood tests that include pancreas; the sensitivity figures come from known cancers, not from screening.
Minimal residual disease became measurable in solid tumours, and the DYNAMIC and CIRCULATE trials that followed turned the measurement into a treatment decision.
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.
There are not thousands of cancer genes, and any one patient's tumour is driven by only a few of them. That makes targeted sequencing panels sensible, but because most drivers are lost tumour suppressors, drugs exist for only a minority, which is why the same group turned to early detection.
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.
It put RNF43 on the pancreatic driver list and gave cyst fluid testing a way to separate the harmless serous cyst from the mucinous ones that need watching.
Shares Genetic instability in colorectal cancers, Distant metastasis occurs late during the genetic evolution of pancreatic cancer, Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability, Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways.
Shares Detection and localization of surgically resectable cancers with a multi-analyte blood test, Core signaling pathways in human pancreatic cancers revealed by global genomic analyses, DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
Shares Detection and localization of surgically resectable cancers with a multi-analyte blood test, DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Liquid biopsy (ctDNA).
Shares The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Liquid biopsy (ctDNA), Colorectal cancer.
Shares Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer, DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer, Liquid biopsy (ctDNA), Colorectal cancer.
Shares Genetic alterations during colorectal-tumor development, Somatic mutation theory of cancer, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Colorectal cancer.
Shares Genetic alterations during colorectal-tumor development, Wnt / β-catenin, Colorectal cancer.
Shares Detection and localization of surgically resectable cancers with a multi-analyte blood test, The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers, DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms, Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.