In situ gene therapy for prostate cancer.

The natural history of prostate cancer presents a dilemma for those interested in developing effective treatment for the disease. When the disease is localized (and therefore potentially curable by localized therapies), it is often of uncertain biological potential and in many cases will not progress to clinical significance. However, both experimental and clinical studies indicate that prostate cancer can metastasize early and/or from relatively small foci of prostate cancer within the gland and is often systemic at the time of diagnosis. Unfortunately, there are no curative therapies for metastatic prostate cancer. In general, currently used therapies with the potential to be curative involve a single cytoablative modality (radical prostatectomy and irradiation therapy) and are directed exclusively at the malignant cells within the prostate gland. At present the widespread use of these treatments alone has not resulted in substantial reduction in mortality from the prostate cancer. Gene therapy used alone or as an adjuvant approach could, at least conceptually, provide a rational solution for the prostate cancer dilemma. With gene therapy, it may be possible to treat localized and systemic disease effectively and simultaneously. Indeed, in situ gene therapy protocols in which viral vectors are used to transduce specific genes that generate cytotoxic activity and/or systemic immunity to the cancer offer hope for significantly reducing the mortality from this disease. This commentary discusses early studies specifically aimed toward developing in situ-based gene therapies that can generate cytotoxic activities in localized prostate cancers and/or the generation of an immune response in the primary tumor that would affect systemic disease.