Prostate Cancer
About Us: Prostate Cancer Center of Excellence
The large scope of activities represented by PCCOE members defies easy categorization. However, much of it falls in three broad areas:
Chemoprevention
Chemoprevention includes both the prevention of cancer and of recurrence. Chemopreventive activities focus on two agents, soy and vitamin J. Mark Cline, DVM, PhD, Department of Comparative Medicine, and colleagues are examining whether men who are supplemented with soy protein with isoflavones have a decreased risk of prostatic cell proliferation than men who are treated with placebo. This research, conducted within the Section on Comparative Medicine, is complemented by ongoing studies of soy on the behavioral and glandular function of macaque monkeys. Human trials using soy in conjunction with vitamin D capitalize on findings from the laboratory of Scott Cramer, PhD, which have showed striking synergy in antiproliferative effects on prostate cancer cells when these agents are administered together. Dr. Cramer’s lab is also actively involved in studies of the role of vitamin D in the differentiation of prostate cancer stem/progenitor cells. An analog of the hormonal form of vitamin D, paricalcitol, is also under investigation in men with metastatic prostate cancer based on the observations made by PCCOE members that paricalcitol inhibits the progression of prostate cancers in the laboratory and clinic.
Genetic Epidemiology
The genetic epidemiology of prostate cancer is the subject of numerous studies, many of which are led by Jiangeng Xu, PhD, MD, who directs the Center for Cancer Genomics. These include studies of genetic susceptibility as well as somatic genetic and epigenetic alterations in prostate tumors. Dr. Xu made important contributions to prostate cancer genetic epidemiology of prostate cancer, including the identification of the first prostate cancer susceptibility gene, HPC1. Gary Schwartz, PhD, and colleagues showed that men whose serum calcium is in the high normal range are at a 2 to 3 fold increased risk of subsequent fatal prostate cancer.
Novel Therapies
Progress in basic science and in epidemiology has facilitated the development of novel experimental therapies within the PCCOE. These approaches include the use of genetically engineered vesicular stomatitis virus to kill prostate cancer cells, an area in preclinical development by Doug Lyles, PhD, and Miriam Ahmed, PhD. William Gmeiner, PhD, and colleagues are developing new drugs and novel strategies for drug delivery. Their discovery of novel polymeric form of fluoropyrimidines that are more potent and less toxic than conventional members of this class of drugs led to exciting developments in preclinical models.
Progress in understanding intermediary metabolism of prostate cancer cells, such as the fatty acid synthesis pathway under investigation in the lab of Steven Kridel, PhD, is likely to identify new targets for novel therapies. Novel therapies exploiting the roles of calcium and parathyroid hormone have been spearheaded by Dr. Schwartz, who is actively recruiting for a trial of the vitamin D analogue, paricalcitol, to suppress parathyroid hormone in men with metastatic prostate cancer (funded by the American Cancer Society), and a trial of Sensipar (cinacalcet hydrochloride) to retard disease progression in men with recurrent prostate cancer.