The Role of Intermediary Metabolism and Molecular Genetics in Prostate Cancer

It is estimated that ̃ 220,000 males in the U.S. will be diagnosed with prostate cancer (PCa) of which ̃ 27,000 will die from this cancer in 2007. African-American males will account for ̃ 37% of the prostate cancer cases and ̃ 31% of the prostate cancer deaths. Once, the malignancy advances to the androgen-independent and metastatic stages, it is untreatable and results in death. The principal factor in the prevention of deaths and morbidity due to prostate cancer is its early detection. Presently, no simple, non-invasive, and reliable screening test exists for early detection of prostate cancer, and this includes the prevalent use of prostatic specific antigen (PSA) testing. There is neither any protocol for the prevention of prostate cancer nor for the treatment of advanced-stage prostate cancer. A major problem in resolving these issues is the lack of understanding of the cause and factors associated with the pathogenesis and progression of prostate malignancy. Despite the voluminous reports and studies from decades of research, the genetic/molecular/hormonal basis of prostate malignancy remains largely unknown, as is also the case for the environmental and dietary influences.

Among the factors and conditions involved in the development of malignancy, the alteration in cellular intermediary metabolism provides the bioenergetic and synthetic requirements of malignant cells. In the absence of altered metabolism, the neoplastic cell will not manifest its malignant potential and will remain in a dormant state or will die. Such a relationship is represented in the development of prostate cancer. In this chapter we will describe the important role of altered intermediary metabolism of prostate cells in the pathogenesis of prostate adenocarcinoma and the progression of malignancy. We present the overwhelming clinical and experimental evidence that implicates the metabolic transformation of citrate-related metabolism as an essential step in the process of prostate malignancy, and its implications on cellular bioenergetics, cell growth, apoptosis, and lipogenesis. The important role of zinc in the metabolic alteration in malignant cells is also presented. A genetic basis for prostate cancer is evolving based on the metabolic implications in the development of malignant cells. Based on metabolic considerations, new concepts concerning the pathogenesis, diagnosis, and treatment of prostate malignancy are presented.