Hormone Depletion Activates Tumor Survival Process in Prostate Cancer, Study Shows

Hormone Depletion Activates Tumor Survival Process in Prostate Cancer, Study Shows

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.

4 comments

  1. Stephen B. Strum, MD, FACP says:

    First, reading the news brief is not the same as reviewing the full text paper–so I apologize for this possibly myopic commentary. I specialize in prostate cancer for the last 34 years and treat patients at all stages of disease. androgen deprivation therapy (ADT) is a main-stay of PC treatment but all ADT therapies cannot be equated. For example monotherapy with an anti-androgen is not the same as LHRH-A + an anti-androgen or a combination of the latter two drugs with a 5-alpha reductase inhibitor (5-ARI) to ↓ DHT production. Testing the patients sensitivity to ADT using an ultrasensitive PSA assay as the “stress test” & mandating that androgen sensitive PC should respond with a PSA < 0.05 is a reasonable strategy. Scholz M, Lam R, Strum S, et al: Prostate cancer-specific survival and clinical progression-free survival in men with prostate cancer treated intermittently with testosterone inactivating pharmaceuticals. Urology 70:506-510, 2007. PMID 17905106. Moreover, ADT induces osteoclast activity with the release of bone-derived growth factors & if this issue is not addressed by monitoring bone resorption markers (BRMs) then the therapeutic index of ADT is diminished. Affecting the epigenetics of PC patients by paying attention to lipids, post-prandial blood glucose and fatty acids is often not done & that too can affect ADT response and possibly the ↑ in PARP. We physicians tend to repeatedly try to throw the "baby" out with the bathwater. We talk about personalized medicine but it is often not done with any sense of due diligence. But I digress and will have to obtain the full PDF–which, BTW, is open access.

  2. Judith Cohen says:

    1 am grateful for all of the information you send me.I have not received your comments on molecular profiling. Do you have any information on this. Regards Judith

  3. Barry Braker says:

    I am not sure how what is being said in this article applies to my circumstance or instance of prostate cancer. I took hormone treatments for 8 years after having my prostate removed in October 2000, at age 49. The cancer had spread to the lymph nodes in my belly area and so they were removed also and now in 2017 I have been cancer free BUT, I must say as I always do “knock on wood”! Thankfully my PSA has been consistent at less than 0.1 and my testosterone level since stopping the hormone treatment has remained at 3, yes that’s correct just three, after I stopped the hormone treatment in approximately 2008 or 2009. I went in to get checked for testosterone treatment and when I asked if would feed the cancer if I boost my testosterone, I was told possibly yes, and so here I sit now thankfully alive, but with a total lack of energy and strength, and insleep a long time each day. So this is where I stand and I don’t understand how your are article will apply, or not to me. Maybe you could enlighten me thank you.

    • Magdalena Kegel says:

      Hi Barry,
      It is difficult for me to say how this research applies to your particular situation. I am not a physician, and as Dr. Strum commented below, hormone deprivation in prostate cancer has complex actions on your body and the a prostate cancer.

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