It is hoped the new discovery, described as a world first, could help stop the spread of the disease and prevent patient relapses.
Ulster University academic Dr. Declan McKenna, who led the study, said: "This new discovery is hugely significant."
For most, a five-year survival rate is just under 90% but for men diagnosed with advanced stage four cancer, the five-year survival rate is only 22%.
However, researchers have found that combining an existing hormone therapy, known as androgen deprivation, with a new drug called OCT1002, can improve treatment effectiveness.
It works by targeting more resistant cancer cells and preventing malignancy and spread.
Dr. McKenna added: "Hormone therapy is an effective treatment but its success with more resistant cancer cells is limited.
"By combining hormone therapy with this new drug we have for the first time discovered a way to destroy these resistant cells that may otherwise lead to relapse or the spread of cancer cells."
The new research builds upon Ulster's University's discovery earlier this year, that low oxygen levels in prostate cancer tumours are responsible for triggering genetic changes.
Those changes accelerate the growth of new cancer cells and can cause patients to relapse within two years of starting the traditional hormone therapy treatment.
"Our next step is to consider a move to clinical trials so we can focus on testing this combined therapy and ultimately develop tailored treatments for individual prostate cancer patients globally," said Dr. McKenna.
The three-year Ulster University study was supported by Prostate Cancer UK, through a £213,000 grant from the Movember Foundation.
The latest results have been published by the journal, Clinical Cancer Research.