Ursula Matulonis, MD :: Profile
Medical Director and Program Leader,
Gynecologic Oncology Program Dana-Farber Cancer Institute
Associate Professor of Medicine
Harvard Medical School
Q: Tell us about yourself as a scientist and how you became interested in cancer research. Did you ever seriously consider another kind of career than that of the sciences?
A: Growing up, I always envisioned myself becoming a physician. This probably dated back to my mother, who wanted to be a doctor when she was a child but wasn’t allowed to go to medical school. I attended a six-year B.S./M.D. medical program and, after graduation, did my internal medicine residency at the University of Pittsburgh. At Pitt, I discovered that I really was interested in leukemias and malignant hematology. I then did my oncology fellowship at Dana-Farber Cancer Institute in Boston, which broadened my exposure of oncology to solid tumors.
Directly after my fellowship, I ended up staying at Dana-Farber and saw both breast and gynecological (GYN) cancer patients. In 2004, I was asked to lead the GYN cancers program at Dana-Farber. I saw an opportunity in GYN cancers to make progress because gynecologic malignancies have been understudied compared to other cancers such as breast cancer.
I think it’s important for the science of GYN cancers to catch up to breast cancer where there have been important strides in just a few short years. And when you look at all the GYN cancers, including ovarian, cervical, and endometrial (uterine) cancers, unfortunately, the survival rates have not substantially changed in over a decade. We are making progress, but it’s slow. So there’s so much work to be done in GYN cancers. This is what excites me about coming to work every day.
So, did I seriously consider another kind of career? No, I never did. But my career has taken on different twists and turns over time, and what I’m doing now is not what I thought I’d be doing when I was back in med school.
Q: Describe your BCRF-funded research project. What are some lab and/or clinical experiences that inspired your work and research focus on the link between ovarian and breast cancers? What are your primary goals for this research?
A: This project, made possible by BCRF’s grassroots supporters affiliated with Play for P.I.N.K., resulted from a longstanding research interest of mine. It involves the study of the BRCA1 and BRCA2 genes, which affect both ovarian and breast cancer risk.
The ovarian cancer subtype called "high-grade serous cancer" is the most common type of ovarian cancer, and it’s also very sensitive to platinum drugs, such as carboplatin and cisplatin. Women who are diagnosed with high-grade serous cancers tend to have a higher chance of having an inherited BRCA 1 or 2 mutation. Also, a subtype of breast cancer called triple negative breast cancer is seen more commonly in women with inherited BRCA mutations.
I work closely with Dr. Judy Garber, a colleague of mine at Dana-Farber and also a member of BCRF's Scientific Advisory Board. She pioneered the use of cisplatin for triple negative breast cancer patients showing excellent response rates, paralleling the results of the use of platinum drugs in high-grade serous cancer of the ovary. These clinical observations prompted my colleagues and me to look at the genetic similarities between triple negative breast cancer and high-grade serous ovarian cancer.
We focused on the loss of heterozygosity (LOH), which provides a sense of the genetic instability of the cancer. We found that the higher LOH, the more sensitive that cancer is to platinum. This means that the patient whose cancer has higher LOH tends to benefit more from platinum chemotherapy and has a better outcome than someone with low LOH.
Our study is important because it may be a way of helping clinicians predict the sensitivity of cancers to platinum drugs, and this really weaves together the genetic similarities between triple negative breast and high-grade serous ovarian cancer.
Currently, with our new grant from BCRF, we are examining LOH as it relates to PARP inhibitors. These are drugs that block a cancer cell’s ability to repair its DNA. These drugs appear to be very effective for women with high-grade serous ovarian cancer, particularly in BRCA mutation carriers. PARP inhibitors do show promise in breast cancer but they haven’t been studied as much in breast cancer. We’re asking the question why some ovarian and breast cancers respond very well to PARP inhibitors and why some don’t.
Q: Are there specific scientific developments and/or technologies that have made your work possible? What additional advances can help to enhance your progress?
What has helped is the price drop in doing gene sequencing and other genetic studies. I think the price tag of laboratory procedures coming down is certainly a good thing. Whole genome sequencing is still very expensive, but for many of these genetic tests, the price decrease will help scientific progress since research budgets are being cut because of reduced grant funding, especially from government sources.
What is also important is how team science has really helped scientific developments move forward faster. One example is a trial combining the use of PARP inhibitors with a PI3kinase inhibitor that I’m the principal investigator of. This research effort has included many investigators. This trial became possible because of exciting preclinical work that these scientific teams were able to accomplish thanks to the help of BCRF and other non-profits. We were able to leverage that data, even before it was published, to approach two pharmaceutical companies and ask for the drugs to run this trial. Today, everyone understands the importance of collaboration and not working in a vacuum anymore.
Q: What direction(s)/trends do you see emerging in cancer research in the next 10 years?
We need to focus more on understanding how cancer cells become resistant to different drugs, and we need to pin down why that happens. We have to be able to detect treatment resistance at the earliest point possible so the next most effective treatments can be selected for individual patients and we can stay one step ahead of the cancer.
I also think that the importance of team science and collaboration will continue. Scientific teams need to include a variety of members such as basic scientists, translational investigators, patient advocates, and clinicians so that all areas of expertise are represented. This collaboration extends not only to individual scientists and medical institutions, but also to pharmaceutical and biotech companies. All of us, including companies and academic centers, will need to work together if we are going to beat cancer.
Q: What other projects are you currently working on?
A: My team at Dana-Farber is also looking at other novel combinations of biologic agents that may be more powerful from an anti-cancer standpoint compared to either agent alone and can possibly overcome mechanisms of resistance.
Another project I am working on along with a large team of scientists at Dana-Farber is growing human ovarian cancer cells in laboratory models. For many years, our group at Dana-Farber has been collecting samples from our patients with ovarian cancer who develop ascites, which is excess abdominal fluid. With the patients’ consent at the time ascites is removed, their ascites are collected and the cancer cells retrieved are then frozen. After the cells are thawed at a later date, these ovarian cancer cells are injected into models and we’ve successfully been able to grow them. We’re now starting to test different combinations of targeted agents. Our ultimate goal is to devise interesting and successful combinations of agents to serve as a preclinical basis/data for a future clinical trial.
Q: How close are we to preventing and curing various forms of ovarian and/or breast cancer?
To prevent ovarian cancer, we may have a potential avenue besides the standard of care for BRCA-carriers, which involves surgery to remove both ovaries and fallopian tubes. Dr. Ronny Drapkin at Dana-Farber is now studying how a normal fallopian tube can become cancerous. As a way of preventing ovarian cancer in high risk women (i.e. BRCA mutation carriers), it may be possible to remove just the fallopian tubes, instead of both the ovaries and tubes, which is the standard practice today.
Obviously this has to be studied better to make sure it’s safe and effective, but this may be the future. This approach may simultaneously reduce a woman’s risk of developing ovarian cancer and also save her from going through extensive surgery and significant side effects, such as early menopause especially in younger patients.
Curing cancer will be harder but is something we all need to strive for.
Q: In your opinion, how has BCRF impacted cancer research?
In this day and age of reduced funding, I often see scientists leaving labs, some labs cutting back personnel, young scientists migrating to companies where jobs are available, or young and even older scientists leaving science altogether. This is happening is because funding has greatly diminished for their research. The sequestration and the NIH budget cuts are having a significant impact on scientific and medical progress for this generation and the next generation, because we are losing people who are doing really good science.
We are poised to make huge advances in cancer treatment, and the timing of NIH budget cuts couldn’t come at a worse time. So for BCRF to have such a pure motive and give such high percentages of its revenue back to science and researchers, is truly impressive. BCRF is allowing researchers to keep doing their important work and is emphasizing the message that funding science leads to improved cancer treatment. It’s important for donors to understand the importance of BCRF and how crucial this organization is for finding better cancer treatments that will eventually one day lead to eradication of breast and other cancers.