We are studying the molecular genetics of human renal cell carcinoma, evaluating the effect of anti-growth factor agents on human genitourinary tumors and participating in studies of adoptive immunotherapy in patients with advanced malignancies. We have identified DNA sequence deletions in the short arm of chromosome 3 in both sporadic as well as a familial form of human renal cell carcinoma which indicate the presence of a renal carcinoma recessive oncogene at this location. We have also identified DNA sequence deletions at chromosomes 11, 17 and 13 at the retinoblastoma locus as well as at the NM23 site and have demonstrated that chromosome 3p retained in the renal tumors were inherited from the affected parent, consistent with our data that the RCC gene is located on chromosome 3p and that 3p loss represents the second step of a two-mutation process. The DNA sequence deletions observed at other chromosomal loci (11, 13 and/or NM23) may be important in progression or metastasis. We have evaluated patients at risk for familial renal cell carcinoma and have demonstrated that the VHL disease gene is located on the short arm of chromosome 3. We have developed, also in collaboration with Dr. B. Zbar, a procedure utilizing a molecular evaluation of lymphocytes which is over 95% accurate -in detecting among at risk individuals who is affected with the familial form of renal cell carcinoma. In evaluating the effect of suramin on human genitourinary tumors we have found that this agent inhibits in vitro proliferation of human prostate carcinoma and that in an suramin plus TNF is more effective than either agent alone. We are currently evaluating the effect of suramin on growth-factor induced mitogenesis in these cells and on the molecular events associated with suramin-inhibition of prostate carcinoma growth. In collaboration with Dr. C.E. Myers of the Medicine Branch we have found that this agent has antitumor activity in patients with advanced hormone refractory prostate carcinoma. We evaluate and participate in treatment of patients with advanced renal cell carcinoma with IL-2 based immunotherapy and have characterized the use of cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 based therapy.
