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School of Medicine
Department Affiliation: Sidney Kimmel Comprehensive Cancer Center; Pathology
Degree: M.D., Johns Hopkins University
Rank: Clayton Professor of Oncology and Pathology
Telephone Number: 410-955-8878
Fax Number: 410-955-0548
E-mail address: email@example.com
School of Medicine Address: Room 589, Cancer Research Bldg., 1650 Orleans Street, Baltimore, MD 21231
Molecular genetics of human colorectal cancer.
The goal of our research is to develop new approaches to the prevention or treatment of cancers through a better understanding of the genes and pathways underlying their pathogenesis.
Our major focus is on cancers of the colon and rectum. We have shown that each colon neoplasm arises from a clonal expansion of one transformed cell. This expansion gives rise to a small benign colon tumor (called a polyp or adenoma). This clonal expansion and subsequent growth of the tumors appears to be caused by mutations in oncogenes and tumor suppressor genes, and the whole process is accelerated by defects in genes required for maintaining genetic instability. Mutations in four or five such genes are required for a malignant tumor to form, while fewer mutations suffice for benign tumorigenesis. As the mutations accumulate, the tumors become progressively more dangerous.
Current studies are aimed at further characterization of the mechanisms through which these genes act, the identification of other genes that play a role in this tumor type, and the application of this knowledge to patient management. Genetic tests for risk assessment, pre-symptomatic detection of tumors, and prognosis have been devised and are constantly being improved. Novel therapeutic agents that target the specific defects in cancer are under development.
- Fearon, E.R., and Vogelstein, B. A genetic model for colorectal tumorigenesis, Cell 61:759-767, 1990. Pub Med Reference
- Kinzler, K.W., and Vogelstein, B. Lessons from hereditary colorectal cancer, Cell 87:159-170, 1996. Pub Med Reference
- Lengauer, C., Kinzler, K.W., and Vogelstein, B. Genetic instabilities in human cancers, Nature 396:643-649, 1998. Pub Med Reference
- Vogelstein, B., Lane, D., and Levine, A.J. Surfing the p53 network, Nature 408:307-310, 2000. Pub Med Reference
- Vogelstein, B. and Kinzler, K.W. Cancer genes and the pathways they control, Nature Medicine 10: 789-799, 2004. Pub Med Reference
- Cheong, I., Huang, X., Bettegowda, C., Diaz Jr. L.A., Kinzler, K.W., Zhou, S. and Vogelstein, B. A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science 314: 1308-1311, 2006. Pub Med Reference
- Wood, L.D., Leary, R,J., Shen, D., Boca, S.M., Barber, T., Ptak, J., Silliman, N., Szabo, S., Dezso, Z., Ustyanksky, V., Nikolskaya, T., Nikolsky, Y., Karchin, R., Wilson, P.A., Kaminker, J.A., Zhang, Z., Croshaw, R., Willis, J., Dawson, D., Shipitsin, M., Willson, J.K.V., Sukumar, S., Polyak, K., Park, B.H., Pethiyagoda, C.L., Pant, P.V.K., Ballinger, D.G., Sparks, A.B., Hartigan, J., Smith, D. R., Suh, E., Papadopoulos, N., Buckhaults, P., Markowitz,S.D., Parmigiani, G., Kinzler, K.W., Velculescu, V.E. and Vogelstein, B. The genomic landscapes of human breast and colorectal cancers. Science 318: 1108-1113, 2007. Pub Med Reference
- Diehl, F., Schmidt, K., Choti, M.A., Romans, K., Goodman, S., Li, M., Thornton, K., Agrawal, N., Sokoll, L., Szabo, S.A., Kinzler, K.W., Vogelstein, B. and Diaz Jr., L.A. Circulating mutant DNA to assess tumor dynamics. Nature Medicine 14: 985-990, 2008. Pub Med Reference
Other graduate programs in which Dr. Vogelstein participates: