Top Docs Q&A: Ursula Matulonis

She just received a $900,000 grant to test new combinations of drugs for ovarian cancer

This post is part of our Top Docs Q&A series where we ask a physician who was selected as one of our Top Docs questions about their field, life as a doctor, and practicing in the Greater Boston area. 

Name: Ursula Matulonis

Hospital Affiliation: Dana-Farber Cancer Institute 

Title: Medical director of gynecologic oncology at Susan F. Smith Center for Women’s Cancers; associate professor of medicine at Harvard Medical School

Field: Medical oncology

Specialty: Gynecological cancers

In January 2014, Ursula Matulonis and her team of researchers received a $900,000 grant from the Ovarian Cancer Research Fund to test new combinations of targeted therapies for ovarian cancer.

Why did you choose the field of women’s and gynecological cancers?

After my fellowship, I started off in a lab working on leukemia, and I really missed clinical work. That’s where I made the move into women’s cancers [gynecological and breast cancers], because I think at that point it was in the mid 1990s and women’s cancers really needed more attention. By 2003 or 2004, I made the decision to focus solely on gynecologic cancers.

What do you love most about working in gynecologic cancers? 

I love our patients, and that there’s a real need to make improvements in the field. Think about the many other types of cancers; treatment options weren’t very significant a few years ago. Yet, with just with focus, effort, research, and out-of-the-box thinking, there have been significant improvements made. We need to make sure that that happens in ovarian cancers as well.

What is the best part about practicing in Boston?

I deal with such an intelligent patient population. They do their homework so we can have intelligent conversations about their options. I also love that my colleagues and I are all concentrated within the city, and that makes it easier to walk from one building to another and actually see people. Our mission is clear every single day, because the researchers aren’t squirreled away in some building miles away; they actually see the patients. I think that constant collaboration with highly intelligent individuals is really terrific.

How has this field changed over the last decade?

It’s changed even in the last two or three years. Specifically for ovarian cancer, we now know that there are different subtypes that exists, and that [the subtypes] act differently with different therapies. Over the past several years the molecular underpinnings of these cancers have become more understood, which has driven clinical trial development that focuses on these different histologic and molecular subtypes.

What are the latest advancements happening in ovarian cancer research? 

We are currently testing drugs called PARP inhibitors; they are quite active in treating high-grade serous ovarian cancers, about 75 percent of women who are diagnosed with ovarian cancer have this subtype. For high-grade cancer the cell has a real inability to repair its DNA when it’s been damaged, and the PARP inhibitor exploits that. There have been several clinical trials, several FDA registration trials, that have been ongoing with the hope that PARP inhibitors will be the first drug that gets an FDA approval since 2006, which is the last time a drug has been approved for ovarian cancer.

You were quoted saying that treatment advances in ovarian cancer have reached a plateau. Why do you think that?

I think it’s a plateau with chemotherapy. Chemotherapy isn’t going away but I think we are kind of at a new phase of ovarian cancer therapies. That major sort of paradigm treatment change hasn’t occurred yet, but I think it will occur with PARP inhibitors, even more so when combining different therapies, because you are not just relying on one pathway. We know cancer cells are very smart, so targeting these different pathways makes sense.

What do you hope for the future of ovarian and gynecological cancers?

Well my hope is that we will be able to understand the cancer’s genetic profile when someone is newly diagnosed and to tailor our therapies in a rational way that has the highest chances of success in our patients. I hope that we can cure more women with ovarian cancer.

Why do you believe target therapies are important for the future of treating gynecological cancers?

You have to break the cancers down into the histologic subtypes because each of them has different sensitivities to different agents and different sort of Achilles’ heels. Chemotherapy has side effects on women with current ovarian cancer, so it has certain limitations. The purpose of this recent grant from the Ovarian Cancer Research Fund is to really use different biologic agents in combination with one another that exploit different problems with the ovarian cancer cell. I think it’s really a new paradigm shift on how we are thinking of ovarian cancer.

Your research also explores the connection between breast and ovarian cancer. What have you found?

There are similarities to a type of breast cancer called triple negative breast cancer and high-grade serous ovarian cancer. We know there are a lot of clinical and molecular parallels with these cancers. For example, these are the types of cancers that are diagnosed in women who have a germline BRCA1 or BRCA2 mutation. So, I’m running a clinical trial that is employing the PARP inhibitor called olaparib, with a drug called a PI3K inhibitor in patients with either triple-negative breast cancer or high-grade serous ovarian cancer. One of my collaborator’s mouse models showed that these two drugs worked better together then individually. 

In January, your team received a grant for $900,000 from the Ovarian Cancer Research Fund, what do you think set your research apart from others for the grant committee? 

We have the mouse models to do it, we have human evidence in our patients that combinations of these different biological agents definitely work, and it we showed that we were really going to do it in a very systematic way. When I found out we got the grant, I was little surprised because it’s a pretty competitive, but it really reinforced that others thought what we were doing really made clinical sense. There is real clinical basis for this work, so it’s not just something we are dreaming up. I do think it’s going to work.