The morning session covered "Hot topics in GU Cancer Biology and Translation with Focus on Translation; Translating Insights about Prostate Cancer Origins to Therapy". In the initial presentation, Dr. Reiter presented data on Prostate Stem Cell Antigen (PSCA) as a therapeutic target for prostate cancer (CaP). He pointed out that cancer stem cells are tumorigenic whereas progeny are not. Dr. Reiter stated that stem cells should be identified and serves as a target for therapy. He stated that PSCA is involved with growth and regeneration in the prostate. PSCA is expressed by virtually all early CaPs, but expression is greater in tumors that are metastatic and likely to recur. Antibodies against PSCA have significant anti-tumor activity in pre-clinical models. A monoclonal antibody against PSCA has been humanized and more recently a pure human antibody has been engineered that is in Phase I trials. The humanized antibody traffics to human tumors in mice and has >50% inhibition of growth. The human antibody has similar activity and is under development with Merck Pharmaceuticals. The Phase I trial is opening at Memorial Sloan Kettering Cancer Center and at Johns Hopkins University. Another use of PSCA is the development of an I-124 "minibody" used for microPET imaging to detect CaP disease recurrence and progression.

Dr. Angelo deMarzo, Johns Hopkins University discussed inflammation and prostate progenitors involved in the induction of CaP. Diet, for example is shown in Japanese who relocate to North America to result in a much higher incidence of CaP compared to men residing in Japan. He described several genes whose function is to mount effective response to infections that are impaired. These include MSR-1 and RNAS-L. Dr. deMarzo described how inflammation results in damaged cells being replaced by increased proliferation. A yet not clearly identified cell located near the basal layer may be involved in the increased proliferation resulting from inflammation. These cells seem to stain positively for PSCA. Three genes; p27, PTEN and NKX3.1 are decreased during this process. GSTP1 methylation is increased in the inflamed environment. Another factor is heterocyclic amines (Phips) from charred meats that cause ventral lobe CaP in a rat model. This dietary carcinogen induces an inflammatory response, thus linking it to models of inflammatory progenitors.

Written by Christopher P. Evans, MD, a Contributing Editor with UroToday.

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