Lipid pathway deregulation in advanced prostate cancer

Area of Science:

• Oncology
• Metabolic pathways
• Lipid metabolism

Background:

• Prostate cancer (PC) development is strongly linked to lipid metabolism.
• Androgen receptor (AR) plays a key role in lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY, and SCD1.
• Obesity and peri-prostatic adipose tissue (PPAT) are increasingly implicated in PC aggressiveness and mortality.

Purpose of the Study:

• To review the established and emerging roles of lipid metabolism in prostate cancer.
• To highlight the potential of targeting lipogenic pathways for novel therapeutic strategies.
• To discuss combination drug strategies involving metabolic pathway inhibitors and AR pathway inhibitors.

Main Methods:

• Literature review of studies on prostate cancer, lipid metabolism, and obesity.
• Analysis of the involvement of key lipogenic enzymes and transcription factors.
• Examination of current and developing therapeutic agents targeting the lipogenic axis.

Main Results:

• The androgen receptor (AR) is integral to numerous lipogenic processes in prostate cancer.
• Lipid metabolism pathways are crucial in both localized and disseminated prostate cancer.
• Emerging evidence links obesity and PPAT to increased PC aggressiveness and mortality.

Conclusions:

• Targeting the lipogenic axis presents a promising therapeutic avenue for prostate cancer.
• Combination therapies, targeting multiple metabolic pathways (e.g., FASN, CPT1) or combined with AR inhibitors (e.g., SCD1, AR), are likely future strategies.
• Understanding lipid metabolism is critical for developing effective treatments for prostate cancer, particularly in the context of obesity.