Conquering cancer has been the goal of Bert Vogelstein, MD, since he was a teenager in Baltimore. For more than 3 decades, Dr. Vogelstein, Co-Director of the Ludwig Center for Cancer Genetics and Therapeutics and Investigator of the Howard Hughes Medical Institute at Johns Hopkins Medical Institution, has been at work researching the molecular changes that drive malignant tumor initiation and progression. In 1989, Dr. Vogelstein’s studies of colorectal cancer led to his discovery that p53—believed to be an oncogene—was actually a tumor-suppressor gene on chromosome 17p. That research led to the understanding that p53 was involved not just in the development of colon cancer but in most types of cancer.
In February, Dr. Vogelstein was recognized for this early discovery and for his life’s achievements in cancer research with a $3 million Breakthrough Prize in Life Sciences award. The award—which also acknowledged the work of 10 other scientists, many of whom have also done research in the genetics of malignant cell growth—was established by a group of Silicon Valley entrepreneurs, including Anne Wojcicki, the founder of the genetics company 23andMe. Ms. Wojcicki told TheNew York Times that the prize is meant to reward scientists “who think big, take risks, and have made a significant impact on our lives.” (For a complete list of award winners, see “Inaugural Winners of $3 million Breakthrough Prize in Life Sciences Announced,” at ASCOPost.com.)
Recently, The ASCO Post talked with Dr. Vogelstein about how he will use his $3 million prize, the impact of his early research on genomic sequencing, and his current investigations of the prevention and early detection of cancer.
Current Research
There are no restrictions on how you can spend your $3 million Breakthrough Prize in Life Sciences award. How do you plan to use the money?
Some of the money will go to pay for my grandchildren’s education, some will go to support my wife’s passion, which is in early childhood education, and some of it will go to support my current research.
What is the focus of your current research?
Our laboratory is trying to develop genetic tests for the early detection of cancer. One of the major outcomes of the revolution in cancer research is an elucidation of the genetic alterations that are responsible for the onset and progression of cancer. These studies began in the 1980s, and in the past 6 or 7 years have reached a new level by virtue of the ability to examine all the genes at once. Through these genome-wide studies, our team and others have found that there is a small group of common genes and pathways that are altered in different cancers.
In addition to their value for potential therapeutics, we believe that these genes and pathways are equally valuable for their capacity to serve as new diagnostic tools. These tools can be used to track treatment effectiveness, and most importantly, as biomarkers to detect cancers when they are still curable by surgery and adjuvant therapy.
PapGene Test
How will the discovery of the mutations in cancer cells be used to improve the early detection of cancer?
One example is a test that Luis Diaz, Jr, MD [Director of Translational Medicine], Kenneth W. Kinzler, PhD [Professor of Oncology], Isaac Kinde [MD-PhD candidate], and others in our lab developed called the PapGene test. This test relies on the sequencing of DNA obtained from routine Pap tests to detect ovarian and endometrial cancers.
Historically, Pap tests have been remarkably successful in the early detection of cervical cancer, and we reasoned that the same specimens might also be used to search for endometrial and ovarian cancers. In particular, we hoped that neoplastic cells from the ovary or the uterine body would lodge in the cervix and be scraped off as part of a routine Pap test. This turned out to be true.
In a pilot study, the PapGene test accurately detected all 24 endometrial cancers (100%) and 9 of 22 (41%) ovarian cancers.1 The next step will be to extend the test to a larger number of women and validate it. If validated, it might be used to detect uterine and ovarian cancers at a stage when they can be cured by surgery or adjuvant therapy. We are trying to develop similar gene sequence–based tests for gastrointestinal cancer through the examination of stool, bladder and kidney cancers through the examination of urine, lung cancer through the examination of sputum, and other cancers through the analysis of plasma.
In the long run, we believe that the best way to reduce cancer morbidity and mortality is through prevention and early detection. Most major advances in public health come from prevention rather than cure. Plan A should be prevention and early detection, and Plan B, cure, which is, of course, important but should only be followed when Plan A fails. Right now there’s much more emphasis and funding devoted to Plan B than Plan A, and I hope that there can be more of a balance between the two in the future.
Potential Impact
What impact would prevention measures and earlier detection have on cancer mortality?
An article published in Science Translational Medicine2 a year ago showed that if what we know today about the modifiable causes of cancer—such as tobacco smoking, obesity, and physical inactivity—were widely appreciated and acted upon, cancer deaths could be reduced by more than 50%. I think that early detection of cancer has the capacity to easily reduce cancer deaths by 50%. So, if you combine the information that we already know about cancer prevention and early detection and these measures are implemented, I think it’s feasible to reduce cancer deaths in the next few decades by three-quarters. And that’s exclusive of advances in therapy that may allow further reductions in deaths.
While there is obviously still much to be learned, I think we now know at least the outline of cancer pathogenesis, particularly its genetic underpinnings. Cancer is no longer a black box. The path forward is clear, and I think that path needs to be followed, not only for its therapeutic implications, but also for its implications for cancer prevention and early detection. ■
Disclosure: Dr. Vogelstein is a founder of Personal Genome Diagnostics, Inc, a company focused on the identification of genetic alterations in human cancer for diagnostic and therapeutic purposes. He is also a member of the Scientific Advisory Board of Inostics, a company that is developing technologies for the molecular diagnosis of cancer using plasma samples. These companies and others have licensed several patent applications from Johns Hopkins, on which Vogelstein is an inventor. The terms of these arrangements are being managed by the university, in accordance with its conflict of interest policies.
References
1. Kinde I, Bettegowda C, Wang Y, et al: Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med 5:167ra4, 2013.
2. Colditz G, Wolin KY, Gehlert S, et al: Applying what we know to accelerate cancer prevention. Sci Transl Med 4:127rv4, 2012.
