Metabolic regulation of prostate cancer heterogeneity and plasticity

Metabolic reprogramming is one of the main hallmarks of cancer cells. It refers to the metabolic adaptations of
tumor cells in response to nutrient deficiency, microenvironmental insults, and anti-cancer therapies. Metabolic
transformation during tumor development plays a critical role in the continued tumor growth and progression
and is driven by a complex interplay between the tumor mutational landscape, epigenetic modifications, and
microenvironmental influences. Understanding the tumor metabolic vulnerabilities might open novel diagnostic
and therapeutic approaches with the potential to improve the efficacy of current tumor treatments. Prostate
cancer is a highly heterogeneous disease harboring different mutations and tumor cell phenotypes. While the
increase of intra-tumor genetic and epigenetic heterogeneity is associated with tumor progression, less is known
about metabolic regulation of prostate cancer cell heterogeneity and plasticity. This review summarizes the
central metabolic adaptations in prostate tumors, state-of-the-art technologies for metabolic analysis, and the
perspectives for metabolic targeting and diagnostic implications.