Bert Vogelstein: Internationally Renowned Cancer Researcher

Bert Vogelstein, M.D., ranks today, as he has for more than three decades, as the pre-eminent international scientist. The discoveries that led the world to understand that cancer is a genetic disease unfolded one by one in his laboratory. 

 Vogelstein, who is co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and a Howard Hughes Medical Institute investigator is best known for his landmark work in deciphering and explaining the molecular genetic basis of cancer. 

Vogelstein began his career in 1974 studying pediatrics at Johns Hopkins after graduating from its school of medicine. Seeing young children suffer from cancer spurred his interest in cancer research. He spent two years at the National Cancer Institute before returning to Johns Hopkins in 1978 to direct the Kimmel Cancer Center’s molecular genetics laboratory. 

When asked to summarize his discoveries of the last 30 years, Vogelstein says, “Cancer is, in essence, a genetic disease.” But more than 20 years ago, when Vogelstein first cracked open the Pandora’s box that is cancer, revealing first one and then a series of genetic mistakes responsible for colon cancer, it was a foreign concept. Today, his discoveries continue to lead his lab and others around the world in developing genetic tests, diagnostics and therapies for cancer. 

In 1989, Vogelstein’s identification of p53 gene mutations in colon cancer began a tide of research linking alterations in the gene to other cancers. It is now known as the most common gene mutation in all cancers. Vogelstein’s lab then discovered a series of other mutations that lined up like dominoes in a cascade of mutations ending in p53. The difficulty of these discoveries is likened to finding one typographical error within 20 volumes of an encyclopedia and then figuring out how it got there. 

“When it comes to cancer genetics, Bert’s work is on the cutting edge of the cutting edge. He led the world to understand that cancer is a disease of genetic defects and then led the first laboratory in the world to reveal what those defects are,” says William G. Nelson, M.D., Ph.D., director of the Johns Hopkins Kimmel Cancer Center. As a result, Vogelstein was ranked in 2003 as the most highly cited scientist in the world during the previous 20 years, according to the Institute for Scientific Information. 

Vogelstein and his colleagues created many cancer gene tests, including for some rare forms of hereditary colon cancers and,  a stool test to screen for genes linked to more common, sporadic colon cancers, a urine test for bladder cancer, and an endometrial and ovarian cancer test that finds cancer-causing gene mutations in fluids obtained during Pap tests. Another cancer test, called CompCyst, incorporates measures of molecular and clinical markers in cyst fluids and artificial intelligence tools to sort out which people with pancreatic cysts will go on to develop pancreatic cancers. The most recent test, called CancerSEEK, is a first-of-its-kind multicancer blood test that screens for eight common cancer types.  

Vogelstein and colleagues’ 1994 discovery of a genetic defect, called mismatch repair deficiency, was linked to response to a specific type of immunotherapy and played a pivotal role in the historic 2017 FDA approval of the immunotherapy drug pembrolizumab across all cancer types for any cancer that contains the genetic defect. It marked the first cancer drug approval based on a specific genetic profile and without regard to where in the body the cancer started.  

Vogelstein and his colleagues were the first to create genomic maps of cancer, starting with breast and colon cancers. They’ve since mapped scores of other cancer genomes, leading to the discovery of mutations in the IDH1 gene, one of the most prevalent in brain cancer. 

With new, faster computing tools to sequence cancer DNA, Vogelstein’s team completed 88 of the first 100 whole exomic sequences of human cancers. These detailed maps create guides by which scientists can pinpoint characteristics of each person’s cancer and tailor therapies and diagnostics to guide treatment—a growing movement toward precision medicine. 

“The history of medicine shows that when a disease is understood, it eventually becomes manageable,” says Vogelstein. “This understanding truly has been revolutionary, and while we can’t cure polio, a massive heart attack, or stroke, we can prevent them. That is the next revolution—the most important one—to take this knowledge we have gathered and help patients in ways that could only be imagined before.” 

Vogelstein’s previous awards include the American Cancer Society Medal of Honor; the National Academy of Science Jessie Stevenson Kovalenko Medal the David A. Karnofsky Memorial Award from the American Society for Clinical Oncology; the Richard Lounsbery Award from the National Academy of Sciences; the Louisa Gross Horwitz Prize from Columbia University; the Harvey Prize in Human Health from the Technion; the Charles S. Mott Prize from the General Motors Cancer Research Foundation; the Prince of Asturias Award in Technical and Scientific Research, considered the “Spanish Nobel”; and the Breakthrough Prize in Life Sciences. 

Vogelstein was elected to the American Academy of Arts & Sciences and the National Academy of Sciences in 1992, and to the American Philosophical Society in 1995. His advisory roles have included chairmanship of the National Research Council Committee on the Biological and Biomedical Applications of Stem Cell Research and the Board of Scientific Counselors of the National Human Genome Research Institute. He has also held editorial positions at ScienceMolecular CellCancer Cell and The New England Journal of Medicine. 

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