Prostate cancer hormone depletion treatments might, in fact, be boosting cancer growth and making a tumor more aggressive, researchers at England’s University of Surrey found.
Their study, which appeared in the journal Nature Communications, demonstrated that a loss of androgen hormones activates a DNA repair enzyme called PARP, which prevents cancer treatment from being effective.
The insight might reduce relapse rates among patients treated this way, and paves the way for treatment combinations using so-called PARP inhibitors, researchers said.
“Our research shows that anti-hormone treatment could be combined with PARP inhibitor to prevent the progression of the disease,” Dr. Mohammad Asim from the universities of Cambridge and Surrey, and the study’s lead author, said in a press release.
Many cancer treatments work by destroying tumor cell DNA, which prevents the cells from multiplying. PARP is a backup DNA repair system, particularly used by cancers with certain mutations that are common in prostate cancer. When the system is activated, cancer cells are better at withstanding the effects of therapy.
But the imprecise repair done by PARP is also linked to a higher tumor mutation rate, which in turn, is linked to more aggressive disease.
Researchers are currently exploring whether drugs that block PARP — and so, prevent DNA repair — might be effective in certain cancer forms.
The study, “Synthetic lethality between androgen receptor signaling and the PARP pathway in prostate cancer,” first used lab-grown cells to investigate the molecular impact of androgen deprivation on prostate cancer cells.
Their experiments showed that the male sex hormones, signaling through the androgen receptor, keep PARP in a suppressed state. When hormones are lost, the enzyme becomes activated.
But a finding in a lab dish does not necessarily translate into human reality. So to verify their observations, the team set up a prospective study with prostate cancer patients. Participants were split into two groups — one had anti-hormone therapy before radiation treatment, while the other started radiotherapy before hormone depletion. Those who received hormone depletion before radiation therapy had fewer cells dying from the radiation.
Looking at tumor biopsies, the study showed that hormone deprivation impacted DNA repair, which was linked to higher PARP activity in the cells. To further verify this, the team compared PARP levels in patients before and after hormone therapy, and saw that PARP levels increased as a result of the androgen-depleting treatment.
“This early stage study adds to the growing evidence that some men with prostate cancer could benefit from being given PARP inhibitors alongside hormone deprivation treatment,” said Dr. Catherine Pickworth from Cancer Research UK.
“The next step is to carry out clinical trials to test if this treatment combination is safe to use in patients and if it helps more men survive the disease,” she added.