BY HALLIE LEVINE

It ’ s something Mary Guckert , RN , MSN , Vice President and Development Leader , Prostate Cancer , at the Janssen Pharmaceutical Companies of Johnson & Johnson , understands well — on both a professional and personal level . Her research at the company is dedicated to working toward promising treatments for prostate cancer , a disease that has affected her family .

While the overall incidence of prostate cancer in the United States has gone down , the percentage of patients with very advanced , or metastatic , disease has gone up over the last decade , according to the Centers for Disease Control and Prevention . Between 2003 and 2017 , the percentage of patients diagnosed with metastatic prostate cancer increased from four per cent to eight per cent

That ’ s especially troubling because metastatic prostate cancer is almost universally fatal : Fewer than one-third of patients survive five years after diagnosis . Roughly one in 12 harbors at least one gene mutation , such as BRCA1 or BRCA2 . These gene variants dramatically increase the risk of developing prostate cancer , especially life-threatening prostate cancer .

As part of its 10-year legacy in prostate cancer innovation , the Janssen Pharmaceutical Companies of Johnson & Johnson has made it its mission to help these patients . The company is in the midst of clinical trials to potentially bring a new form of prostate cancer treatment to patients with this common gene mutation and a panel of other gene mutations , such as FANCA , PALB2 , CHEK2 , BRIP1 , HDAC2 and ATM , which are actively being evaluated in clinical trials .

We sat down with Mary Guckert to learn about the company ’ s latest research , how it may prove to be promising for metastatic prostate cancer — and the ways her personal passion for working to help eliminate cancer is fueling this critical work .

First of all , what are BRCA mutations , and how do they play a role in prostate cancer ? BRCA1 and BRCA2 are genes that produce proteins that help repair damaged DNA . They are also sometimes called tumor suppressor genes , and when they have certain variants or mutations , cancer can develop . The genes can ’ t repair damaged cells the way they normally would , which allows abnormal cells to replicate unchecked .

If you inherit one of the BRCA mutations , you have increased risk of several different

cancers , including , in some people , prostate cancer , and even if these mutations are not inherited , tumors can also harbor them ..

A 2016 study published in the New England Journal of Medicine , for example , found that risk of metastatic prostate cancer was more common in patients with genetic mutations compared to noncarriers .

What is DNA Damage Repair Factor , and how can it help these patients ? DNA Damage Repair Factor is a type of targeted therapy that helps cells repair themselves from damage . One way to do that for some patients with prostate cancer with a specific mutation is through drugs known as poly ( ADP-ribose ) polymerase , or PARP , inhibitors .

PARP is a substance that plays a key role in the repair of DNA . When you block PARP as part of a cancer treatment , it may prevent cancer cells from repairing their damaged DNA , causing them to die . Studies show that PARP inhibitors can often be a very successful treatment for patients with advanced prostate cancer who also have a BRCA mutation in particular , since their cancer cells are especially sensitive to PARP inhibitors .

Our hope is that by having targeted treatments available early in the disease process for prostate cancer patients with these mutations , we can identify these patients at the time of their diagnosis and potentially significantly improve their outcomes .

But we may also be able to take treatment one step further . While PARP inhibitors that target cancer cells are highly effective , they aren ’ t enough to eradicate the cancer alone . Prostate cancer is a very complicated disease with multiple growth drivers ; the most notable and studied in recent years are androgens . Androgen hormones stimulate prostate cancer cells to grow . It appears that when androgen production is inhibited , DNA repair in cancerous cells slows down .

It makes sense to assume that targeting both pathways in cells may lead to more cancer-cell deaths than targeting either pathway alone . We are evaluating combination approaches that interrupt the androgen-making process as well as impact the tumor ’ s ability to repair DNA to make treatments even more effective .

We ’ re not advocating this combination approach for all patients with prostate cancer at this time but rather taking a personalised approach based on presence of mutation .

Why is there such an urgent need for treatments for this type of prostate cancer ? We know that patients with prostate cancer who have certain mutations face a worse prognosis , but unfortunately there are currently no PARP inhibitor combinations available to them until very late in the disease . We are evaluating the benefits and

Mary Guckert

the risks of giving these combination treatments earlier in metastatic disease progression , before patients receive treatments like chemotherapy .

Current treatment guidelines in the US recommend that all patients with metastatic prostate cancer , and some with localised prostate cancer who have identified risk factors such as a family history of the disease , receive genetic testing .

For example , a survey published earlier this year in the Journal of the Canadian Urological Association found that only a little over a third of oncologists recommended that their patients with newly diagnosed metastatic prostate cancer go for genetic testing . And a recent analysis of more than 5,000 US patients with metastatic prostate cancer found that only 13 per cent had documented genetic testing .

Our hope is that by having targeted treatments available early in the disease process for prostate cancer patients with these mutations , we can identify these patients at the time of their diagnosis and potentially significantly improve their outcomes by providing more personalized treatments at the right time in their treatment journey .

What motivates you to study prostate cancer in particular ? I started my career as a nurse at a major academic hospital and have taken care of many patients who are battling a cancer diagnosis . Oncology nurses focus not just on administering treatments and managing side effects but holistically , on the entire patient experience .

Guckert and her dad

I also have a personal perspective : My father was diagnosed with prostate cancer many years ago , when I was in college . We spent many years holding our breath waiting to receive his PSA blood test results , since a significant rise could mean his cancer had recurred . Fortunately , he is doing well .

Testing for the BRCA gene , in addition to other mutations potentially associated with familial cancers , is something I have undergone personally . In addition to my father , all three of my sisters have had cancer , and two of them have died . While none of us were found to have a genetic mutation of significance , like BRCA , it was important information to gather .

However , there are people out there with certain oncological mutations that we may be able to target with treatment in the future . That ’ s what motivates me to get up each morning and go to work : the belief that our work will allow thousands of people to continue to lead full , productive lives . — The Health

This is an edited version of an article appeared recently on the website of Johnson & Johnson