Oncologist Bert Vogelstein has demonstrated how sequential accumulation of mutations leads to colorectal cancer, and Jan H. Hoeijmakers has conducted breakthrough research in xeroderma, a hereditary disease causing skin cancer.
For the tenth time, the Charles Rodolphe Brupbacher Prize will be awarded in conjunction with an international symposium. The prize of 100,000 Swiss francs for each scientist, is one of the world’s most prestigious honors in cancer research. The prize is awarded every two years to investigators who have made outstanding contributions to oncology. The symposium will also honor five junior researchers who will receive a Young Investigator Award.
This year's Brupbacher Prize goes to Prof. Bert Vogelstein of the John Hopkins University in Baltimore (USA) and to Prof. Jan. H. Hoeijmakers of Erasmus University, Rotterdam (Netherlands). The findings of both researchers have contributed greatly to the understanding of the genetic basis of tumor growth. Bert Vogelstein's main area of research is colorectal cancer, Jan Hoeijmakers' is skin cancer. The particular significance of their findings lies in their general relevance: Cancer of the colon and rectum is closely linked to lifestyle of Western populations and is the second-leading cause of cancer-related deaths in Europe. Hoeijmakers’ findings do not only shed light on skin tumors, but also on premature aging.
Bert Vogelstein ranks among the most-quoted scientists in the field of biomedicine. He is best-known for his groundbreaking work on the genesis of cancer of the colon. Tumors in the large intestine (colon) lend themselves particularly well to analysis because their progression from a benign growth to a malignant tumor can be clinically observed by means of colonoscopies.
Vogelstein has observed that initial, small accumulations of atypical cells are caused by a mutation of the APC gene, a tumor-suppressor gene that controls cell division. The mutation of the APC gene is also responsible for inherited familial adenomatous polyposis, a disease characterized by a great number of polyps in the intestinal wall. If not removed, these polyps can develop into colon cancer.
Additional mutations activate genes coding for growth factors (oncogenes).as well as in other tumor suppressor genes. All of these DNA mutations mediate a slow but steady growth from initially small, then larger benign polyps that then progress into a carcinoma. Although it takes an average of 17 years for a small polyp to develop into a carcinoma, the process then accelerates, leading typically within two more years to a highly malignant carcinoma that metastasizes to regional lymph nodes and distant organs.
Vogelstein's findings on the sequential accumulation of mutations and tumor growth have received wide-spread recognition and provide the basis for prevention, early diagnosis and treatment of colorectal cancer. Vogelstein has recently begun analyzing entire cancer genomes, i.e. the sum of all genes in a cell. Understanding the genetic make-up of a tumor provides the basis for personalized tumor therapy, a major goal in clinical oncology.
Jan H. Hoeijmakers
Jan Hoeijmakers has made an outstanding contribution by elucidating the molecular basis of hereditary diseases caused by defective DNA repair. There are multiple pathways for the repair of damaged DNA. If left unrepaired, this increases the risk of several diseases, including cancer. Dr. Hoeijmakers has performed innovative research on xeroderma pigmentosum, a hereditary skin disease that is characterized by extreme sensitivity to UV rays and the development of multiple, often malignant tumors in skin regions exposed to sunlight. Ultraviolet rays cause damage involving chemical links between coding DNA bases, particularly thymine. During cell division and in the absence of efficient repair, this leads to permanent mutations in daughter cells. Patients affected by xeroderma pigmentosum demonstrate a reduced DNA repair capacity.
Hoeijmakers identified and characterized multiple genes involved in the repair process. He was able to show that certain forms of limited DNA repair capacity can bring about the exact opposite of a tumor, namely premature aging.
A complex DNA repair system ensures the stability of our genome. Jan Hoeijmakers has earned international recognition for having identified key aspects of the molecular basis of DNA repair and the role it plays in both, the development of tumors and in premature aging.The foundation:
Beat Müller | idw
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