Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc, and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low- and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.

The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogramming also plays a significant role in suppressing the immune attack on the tumor cells and in resistance to therapies. Thus, the metabolic cooperation and competition among the different TME components besides the inherent alterations in the tumor cells arising out of genetic as well as epigenetic changes supports growth, metastasis, and therapeutic resistance. This review focuses on the metabolic remodeling achieved through an active cooperation and competition among the three principal components of the TME—the tumor cells, the T cells, and the cancer-associated fibroblasts while discussing about the current strategies that target metabolism of TME components. Further, we will also consider the probable therapeutic opportunities targeting the various metabolic pathways as well as the signaling molecules/transcription factors regulating them for the development of novel treatment strategies for cancer.