Drs. Linehan and Zbar have worked together for more than two decades on determining the molecular basis of kidney cancer in order to provide the foundation for finding more effective treatments. They talked with the NCI Cancer Bulletin about where they have been and where this research is headed.
Can you talk about the role of studying families in your work over the years?
Dr. Zbar: We sent letters to physicians in the United States and Canada to recruit families with hereditary renal carcinoma. Physicians were targeted based on the specific clinical characteristics of the disease under study. I worked with a small NCI team to evaluate renal carcinoma families, which included conducting detailed medical histories and collecting blood samples for DNA analysis at our laboratory at NCI-Frederick.
We then set up a large, multidisciplinary team to evaluate patients. We constructed family trees and performed genetic mapping, then physical mapping in the hope of finding the disease genes. We've seen families from all over this country and, really, all over the world.
After everything that's been accomplished, is it now just a matter of seeing which agents are most effective in clinical trials?
Dr. Zbar: It would be extremely useful to identify molecular markers to determine which patients will be the best candidates for the various targeted treatments. The presence (or absence) and specific type of somatic VHL mutation would be one genetic alteration that might predict response of metastatic renal carcinomas to drug therapy.