Quinolinic Acid Fuels Prostate Cancer Growth and Treatment Resistance

A new study published in Cell Death Discovery has uncovered a key link between quinolinic acid and androgen receptor signalling in prostate cancer. The findings highlight how this metabolite influences disease progression and treatment resistance. Researchers suggest the discovery could lead to novel therapeutic strategies for patients with advanced prostate cancer. The study reveals that quinolinic acid, a product of the kynurenine pathway in tryptophan metabolism, enhances androgen receptor (AR) activity. It does so by promoting AR movement into the nucleus, where it boosts the expression of genes tied to cancer cell growth and survival. This process relies on FDPS, an enzyme in the mevalonate pathway, creating a newly identified metabolic connection in prostate cancer biology.

High levels of HAAO, the enzyme producing quinolinic acid, were found in prostate cancer tissues. These elevated levels are associated with later disease stages and worse patient outcomes. The research also demonstrates that quinolinic acid increases FDPS activity, which in turn strengthens AR signalling and contributes to resistance against standard anti-androgen treatments.

Modulating quinolinic acid levels may improve the effectiveness of existing therapies. The study proposes that combining HAAO inhibitors or agents targeting quinolinic acid synthesis with anti-androgen drugs could prevent or delay resistance. This approach may sensitise cancer cells to treatment, offering a potential new way to tackle the disease. The findings open the door to treatment strategies that pair metabolic inhibition with hormonal therapy. Such combinations could transform outcomes for prostate cancer patients by overcoming resistance mechanisms. The research also encourages investigation into similar metabolic pathways in other cancers.