University of California, Los Angeles (UCLA) researchers have identified a promising strategy to make a new class of targeted cancer therapies more effective against one of the deadliest forms of prostate cancer, potentially overcoming treatment resistance that has, to date, limited their success.

Metastatic castration-resistant prostate cancer is an aggressive form of the disease that no longer responds to hormone therapy and remains incurable despite advances in treatments. 

Currently antibody-drug conjugates (ADCs), precision medicines that deliver potent cancer-killing drugs directly to tumours, have transformed care for several other cancers but have shown only modest and often short-lived benefits in prostate cancer.

But new research, published in the Journal of Clinical Investigation, shows that combining ADCs with a drug that blocks a cancer cell survival protein called BCL-XL can make prostate cancer cells more responsive to treatment. In the laboratory, the combination triggered greater cancer cell death and slowed tumour growth compared with either therapy alone, suggesting a potential new approach for developing the next generation of targeted therapies for advanced hormone-resistant prostate cancer. 

It's essentially a way of delivering chemotherapy with much greater precision said Dr. John Lee, co-senior author of the study. Rather than introducing a single new therapy, we've established a framework to give us an opportunity to better tailor these therapies to advanced prostate cancer.

If the findings are confirmed in future clinical trials, the approach could offer a new strategy for improving antibody-drugs to treat metastatic prostate cancer, where treatment resistance remains one of the greatest challenges.