Quinolinic Acid Fuels Prostate Cancer's Resistance to Treatment, Study Finds

A new study has uncovered how quinolinic acid, a metabolite from the kynurenine pathway, boosts androgen receptor signalling in prostate cancer. The research, published in Cell Death Discovery, highlights a mechanism that may drive resistance to current treatments. Scientists say the findings could pave the way for improved therapies for advanced disease. The study was led by Zhang, H., Feng, T., Lv, M., and their team. They found that quinolinic acid is produced downstream of HAAO, an enzyme elevated in prostate cancer tissues. Higher HAAO levels correlate with more advanced disease and worse patient outcomes.

Using transcriptomics, metabolomics, and functional assays, the researchers demonstrated that quinolinic acid enhances FDPS activity. This, in turn, increases androgen receptor signalling by promoting its nuclear translocation and transcriptional activity. The result is heightened expression of genes that drive cancer cell growth and survival.

The team also showed that blocking HAAO or reducing quinolinic acid production weakens FDPS-dependent AR signalling. This slows tumour growth and makes anti-androgen drugs like enzalutamide more effective. Patient-derived xenografts and clinical data further confirmed these findings, suggesting the approach is ready for clinical testing. The discovery links quinolinic acid to treatment resistance in prostate cancer. Targeting HAAO or quinolinic acid production could enhance existing therapies. Researchers now propose combining these inhibitors with standard anti-androgen treatments for better patient outcomes.