Investigating PLOD2 as a Therapeutic Target to Overcome Metastasis in Radiorecurrent Prostate Cancer

Abstract

Metastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer- related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line. This dissertation investigates the role of PLOD2 in driving tumour progression and metastatic potential in radiorecurrent prostate cancer, with particular focus on identifying clinically feasible methods of inhibition. The work herein reveals PLOD2 as a negative prognostic factor associated with biochemical relapse and metastatic disease in prostate cancer patients, driving in vitro invasion, migration, and in vivo extravasation; treatment with the HIF1α inhibitor PX-478 effectively suppresses this metastatic phenotype in radiorecurrent prostate cancer cells. Together, these results demonstrate for the first time the role of PLOD2 in radiorecurrent prostate cancer invasiveness, and point towards its potential as a therapeutic target to reduce metastasis and improve survival outcomes in prostate cancer patients.