An innovative new drug being trialled to tackle certain cancers could also benefit patients with advanced prostate cancer whose treatment has stopped working, according to scientists.
Experts hailed the discovery as an “exciting step” towards tackling treatment resistance for patients with the disease.
The drug, known as NXP800, works by targeting the heat shock factor 1 (HSF1) pathway, a cellular protective mechanism that is hijacked to support the growth of cancer.
The pathway controls the production of heat shock factor proteins, which are overexpressed in many cancer cells, helping them to cope with stressful conditions as tumours develop.
A team from the Institute of Cancer Research, London, found NXP800 slowed the growth of prostate cancer cells, including those that had developed a resistance to the hormone therapy enzalutamide.
Dr Adam Sharp, leader of the Translational Therapeutics Group at The Institute of Cancer Research, London, and honorary consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said: “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.
“With this research, we’ve shown that targeting the heat shock response pathway – a pathway responsible for enabling tumours to withstand stress and keep growing – is a potential new avenue for treating advanced prostate cancer.
“The pathway impacts the hormone signalling that drives cancer, but it’s not susceptible to the usual mutations that drive drug resistance.
“Excitingly, we’ve shown that targeting this pathway can slow the growth of prostate cancer tumours – even for tumours that are resistant to hormone therapy. The next step will be to assess if certain prostate cancer patients would respond better than others.”
For the study, scientists analysed data from 439 advanced prostate cancer samples and found higher levels of heat shock proteins were associated with more androgen receptor signalling, which drives the development and growth of prostate cancer.
NXP800 was shown to slow the growth of prostate cancer in lab-grown cells, as well as in mini tumours grown from patients samples.
The drug also slowed cancer growth in mice with hormone therapy-resistant prostate cancers.
Without NXP800, all tumours doubled in size in 38 days. When treated with the drug, only 37.5% of tumours reached that size within that time.
Professor Kristian Helin, chief executive at the Institute of Cancer Research, London, said: “Drug resistance is one of the biggest problems we face in treating cancer.
“Finding drugs that can slow down cancer’s growth when all other treatments have stopped working is critical.”
Johann de Bono, regius professor of cancer research at the Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said: “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 been granted designations from the US Food and Drug Administration (FDA) to speed up its development to potentially treat ARID1a-deficient ovarian, fallopian tube, and peritoneal cancers, and bile duct cancer, a rare disease that forms in small tubes that connect different organs.
The Institute of Cancer Research, London, study was backed by Prostate Cancer UK, Movember, and the Prostate Cancer Foundation, and is published in Clinical Cancer Research.
Simon Grieveson, assistant director of research at Prostate Cancer UK, said: “For men with advanced prostate cancer, treatment with hormone therapy can be very effective at delaying cancer progression, however eventually these treatments are likely to stop working.
“This is a critical problem we need to address through continued research into brand new approaches to treating prostate cancer, and this is a fantastic example.
“These findings provide valuable insight into the role of heat shock proteins, which we now know are at a higher level among advanced prostate cancer patients and associated with worse outcomes.
“Targeting these proteins with this novel drug could give men with hormone resistant prostate cancer a new option for treatment and, crucially, more valuable time with their loved ones.
“Clinical trials are now needed, but this is an exciting step towards a new solution to tackling treatment resistance in prostate cancer.”