Searching for suppressor genes in prostate cancer.
Prostate cancer poses many challenges for clinicians. Methods for early detection are not satisfactory, and in fact more efficient detection will lead to even further dilemmas. We know from necropsy studies that the occurrence of prostate cancer is much higher than the clinical incidence (Yatani et al, 1982). Obviously, only some of the prostate cancers detected early would progress to a health threatening state if left untreated--the question is, which ones? This is a question that must be addressed, because prostate cancer has the highest occurrence rate of any cancer among males in the US, and current approaches to eradicating early stage prostate cancers involve expensive surgical or irradiation techniques. Even for primary prostatic tumours of more advanced stages, current prognostic indicators are not ideal. What is the potential of specific suppressor genes lost in prostate cancer for identifying useful prognostic indicators? Even though numerous molecular events, including loss as well as gain of gene activity, have been delineated for colon cancer, no single genetic change has proven prognostic. Rather, increasing malignant potential of colon cancer seems to be correlated with an accumulation of several genetic events. On the other hand, a specific chromosomal abnormality, a deletion of chromosome 17p, does appear to be a prognostic indicator for distinguishing high grade from low grade transitional cell carcinoma (Olumi et al, 1990). Whether loss of chromosome 17p will prove to be a better prognostic marker than other parameters, however, is still unknown. At present, no consistent genetic changes have been associated with any stage of prostate cancer, so we are a long way from determining whether such changes will prove their hypothetical usefulness as new and improved prognostic indicators. The other clinical realm in which the identification of loss of suppressor genes in prostate cancer might prove a resource is therapy. Suppressor gene products obviously provide key regulatory functions, perhaps linked to differentiation, in normal cells. Restoration of these regulatory functions in cancer cells, either by directly supplying the lost regulatory element or by circumventing the missing element by other means, is a novel therapeutic approach that might offer hope even in metastatic disease. Realization of this dream will require much more knowledge of the precise nature of the suppressor gene products lost in cancer, and a detailed understanding of the hierarchy of regulation of growth and differentiation in normal cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Peehl
D M
DM
Department of Urology, Stanford University School of Medicine, California 94305.
D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D016153:Genes, Suppressor / Q000502:physiology*; D006801:Humans; D006822:Hybrid Cells; D066298:In Vitro Techniques; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D013539:Simian virus 40 / Q000472:pathogenicity