An innovative drug, NXP800, currently in clinical trials for ovarian and bile duct cancers, has shown promise in preclinical studies for treating advanced prostate cancer that has developed resistance to hormone therapies. Scientists at the Institute of Cancer Research (ICR), London, reported that NXP800 effectively slowed the growth of prostate cancer cells, including those resistant to enzalutamide.
This research offers a potential new avenue for treating advanced prostate cancer, where drug resistance remains a significant challenge. The study, published in Clinical Cancer Research, was supported by Prostate Cancer UK, Movember, and the Prostate Cancer Foundation.
Targeting the Heat Shock Response
NXP800 functions by targeting the heat shock factor 1 (HSF1) pathway, a cellular mechanism that protects cancer cells from stress as tumors develop. This pathway controls the production of heat shock proteins, which are often overexpressed in cancer cells, aiding their survival. By inhibiting this pathway, NXP800 disrupts the cancer cells' ability to withstand stressful conditions.
Dr. Adam Sharp, leader of the Translational Therapeutics Group at The Institute of Cancer Research, London, explained, "While hormone therapies have extended the lives of lots of men with advanced prostate cancer, drug resistance is inevitable. We need to tackle the problem from a new angle."
Study Findings
Researchers analyzed data from 439 advanced prostate cancer samples and found that higher levels of heat shock proteins correlated with increased androgen receptor signaling, which drives prostate cancer development. The study also revealed that patients with higher levels of these proteins had poorer overall survival, surviving for 22.0 months compared to 33.5 months for those with fewer heat shock proteins.
In lab studies, NXP800 slowed the growth of prostate cancer cells, including those resistant to enzalutamide. In mice with hormone therapy-resistant prostate cancers, NXP800 significantly slowed tumor growth. Without the drug, all tumors doubled in size in 38 days, while only 37.5% of tumors treated with NXP800 reached that size within the same period.
Clinical Implications
Professor Johann de Bono, Regius Professor of Cancer Research at the Institute of Cancer Research, London, noted, "We have shown that people with prostate cancers with higher levels of heat shock proteins have significantly worse outcomes. If targeting these proteins proves effective in clinical trials, patients with advanced prostate cancer will be able to look forward to longer and better quality lives."
NXP800 has already received Fast-Track and Orphan Drug Designations from the FDA for ARID1a-deficient ovarian, fallopian tube, and peritoneal cancers, as well as Orphan Drug Designation for bile duct cancer. These designations aim to expedite the drug's development for rare diseases.
Next Steps
The researchers hope these findings will lead to clinical trials of NXP800 for advanced prostate cancer. Further studies are needed to identify which prostate cancer patients are most likely to benefit from this treatment approach. According to Simon Grieveson, Assistant Director of Research at Prostate Cancer UK, "Clinical trials are now needed, but this is an exciting step towards a new solution to tackling treatment resistance in prostate cancer."
