Figure 3.

Factors shaping prostate cancer metabolism. Prostate cancer metabolism is influenced by factors inside the cancer cell (intrinsic), immediately adjacent to the cancer cell (extrinsic), and derived from multi-system perturbations (systemic). The intrinsic factors (red) represent intracellular changes regulated by androgen receptor (AR) signaling activity, genetic alterations, and therapy resistance. The extrinsic factors (green) are extracellular signals derived from nearby cells that influence cancer cell metabolism and adaptation. These include dysregulated vascularization, acidosis, hypoxia and cancer-associated fibroblasts (CAF), immune cells and peri-prostatic adipose tissue (PPAT), which collectively contribute to the tumor microenvironment (TME). The systemic factors (blue) that regulate tumor metabolism include alterations in the body’s metabolic and hormonal milieu, induced by short-term perturbations or long-term changes in metabolic state, including exercise and obesity, respectively. These complexities should be considered when assessing metabolic changes in prostate cancer and highlight the multiple challenges in implementing metabolic therapies into clinical practice.