Table 1.

Methodological considerations.

Limitations of experimental models used to assess metabolism in prostate cancer
• Most studies assessing metabolic regulation have been conducted in immortalized prostate cancer cells, including PC3, DU145 and LNCaP, which facilitate simple physiological and/or genetic manipulation and high throughput analysis, but bare limited resemblance to the complexity or heterogeneity of human tumors.
• Exposure of cells in vitro to supraphysiological nutrient levels in the culture medium unlikely recapitulate the condition in tumors, although it is noted that the concentration of metabolic substrates in the tumor microenvironment (TME) are currently unknown.
• In vivo studies using genetically engineered mouse models of prostate cancer overcome some of these issues, however the mutations do not replicate the genomic and phenotypic heterogeneity observed clinically.
• The use of human tissues or clinical studies are often impracticable due to limited access to patients under carefully controlled conditions and the technical difficulty in assessing tissue-specific metabolism in vivo.
• To overcome this limitation, prostate cancer patient-derived xenografts (PDXs) capture the heterogenous nature of tumor of origin. However, despite its perceived superiority over other approaches, PDXs lack stroma and immunological contribution.
• Combined approaches that integrate these complementary models are required to understand the metabolic landscape of prostate cancer and identify promising therapeutic strategies.