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Targeting lipid metabolism in metastatic prostate cancer
Tahlia Scheinberg1,2,3, Blossom Mak1,2,3, Lisa Butler4,5
1Medical Oncology, Chris O'Brien Lifehouse, Camperdown NSW, Australia.
Abstract:
Despite key advances in the treatment of prostate cancer (PCa), a proportion of men have de novo resistance, and all will develop resistance to current therapeutics over time. Aberrant lipid metabolism has long been associated with prostate carcinogenesis and progression, but more recently there has been an explosion of preclinical and clinical data which is informing new clinical trials. This review explores the epidemiological links between obesity and metabolic syndrome and PCa, the evidence for altered circulating lipids in PCa and their potential role as biomarkers, as well as novel therapeutic strategies for targeting lipids in men with PCa, including therapies widely used in cardiovascular disease such as statins, metformin and lifestyle modification, as well as novel targeted agents such as sphingosine kinase inhibitors, DES1 inhibitors and agents targeting FASN and beta oxidation.
Insights
Prostate cancer (PCa) resistance to therapies is a major challenge. This review highlights how targeting lipid metabolism, using existing and novel agents, offers new therapeutic strategies for PCa treatment.
Area of Science:
- Oncology
- Metabolic Research
- Pharmacology
Background:
- Prostate cancer (PCa) remains a significant health concern, with resistance to current treatments posing a major clinical challenge.
- Aberrant lipid metabolism is increasingly recognized as a key driver in prostate cancer development and progression.
- Obesity and metabolic syndrome are epidemiologically linked to increased PCa risk and progression.
Purpose of the Study:
- To review the epidemiological associations between obesity, metabolic syndrome, and PCa.
- To explore the role of altered circulating lipids as potential biomarkers for PCa.
- To discuss novel therapeutic strategies targeting lipid metabolism in PCa.
Main Methods:
- Literature review of epidemiological studies, preclinical research, and clinical trial data.
- Analysis of evidence linking lipid alterations to PCa development and progression.
- Synthesis of information on existing and emerging lipid-targeting therapies.
Main Results:
- Significant epidemiological links exist between obesity, metabolic syndrome, and PCa.
- Circulating lipids show potential as biomarkers for PCa detection and monitoring.
- Numerous preclinical and clinical studies support targeting lipid metabolism for PCa treatment.
Conclusions:
- Targeting lipid metabolism represents a promising therapeutic avenue for overcoming PCa resistance.
- Existing cardiovascular drugs (statins, metformin) and lifestyle modifications show potential in PCa management.
- Novel agents targeting specific lipid pathways (e.g., sphingosine kinase, FASN) offer new hope for PCa patients.
