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Integrated Analysis of Proteomic and Genomic Signatures in Blood for Early Detection of Ovarian Cancer
Approximately 22,000 women are diagnosed with ovarian cancer annually in the United States, and unfortunately the vast majority of cases are detected at late stages when cure is difficult to achieve. This is because the symptoms of ovarian cancer are non-specific, too often leading to substantial delays in diagnosis. The development of a non-invasive early detection strategy for ovarian cancer would likely result in dramatic improvements in the prognosis of the disease. Efforts to develop blood tests for ovarian cancer screening have largely focused on detection of tumor-derived proteins in the circulation, but success has been limited because blood levels of such proteins can also be elevated in individuals who do not have cancer. In contrast, small fragments of DNA that are shed into the blood from dying tumor cells contain mutations that are exquisitely cancer-specific. Such mutations would be extremely uncommon in the blood of healthy individuals. However, the levels of such DNA fragments in patients with early-stage ovarian cancer tend to be very low – too low to be detected in the blood of some patients. Thus, we are proposing to develop a test for detecting early-stage ovarian cancer that simultaneously harvests and analyzes tumor-derived DNA fragments as well as several tumor-derived protein markers in the blood. We will build upon several years of collaborative research already undertaken by our laboratories to develop robust methods for analysis of ovarian cancer-specific protein and DNA biomarker panels. By probing for both DNA and protein signatures in the same blood sample, we hope to be able to increase the probability of detecting small, early-stage ovarian cancers while minimizing the chances of having falsepositive test results in women who do not have disease. We believe that this approach of integrating multiple biomarkers holds great promise toward the development of a practical test for ovarian cancer screening.
Q&A WITH ABHIJIT PATEL, M.D.
Q: How would you explain the broader significance of your research to a layperson?
A: We strongly believe that one of the most effective ways to reduce ovarian cancer deaths is to detect it early. Unfortunately, because the symptoms of ovarian cancer are so vague, it is typically discovered at a late stage when cure is more difficult to achieve. So our efforts are focused on developing a blood test that is capable of detecting fragments of tumor DNA that are shed into the bloodstream. By looking for genetic signatures in the blood that are unique to tumors and would be extremely uncommon in healthy individuals, we hope to contribute to the development of a highly specific blood test that could be used to screen for ovarian cancer.
Q: What is the job of a scientific medical researcher on a day to day basis? For example, what did you do this morning?
A: I spent much of this morning discussing results of an experiment with one of my students, and planning the next steps for her project. This is one of the aspects that I enjoy most about my job: having the opportunity to work with like-minded people to come up with innovative ways to solve scientific puzzles. Of course, much of my day is spent in front of the computer, writing grants and papers, so I rarely get the opportunity to perform experiments at the bench myself anymore. But I very much enjoy thinking about science and really delving into the experimental details, so I try to prioritize scientific discussions with my students and postdocs.
Q: Do you feel that Tina’s Wish is a unique organization? What sets it apart?
A: My lab’s research has been supported by Tina’s Wish for several years, so I feel that I have gotten to know the organization quite well. What I think sets it apart is the incredible passion for the cause that I have seen amongst the members of the board. In addition to their fundraising efforts, they are also very involved in facilitating exchange of scientific ideas amongst the grantees to maximize the progress and impact of the research.
Q: Have you formed any valuable or interesting relationships through Tina’s Wish?
A: I have attended several symposia and fundraising events organized by Tina’s Wish, and I am also participating in a collaborative research project supported by the Kirpalani Consortium Grant. Through these activities, I have gotten to know the other grantees as well as the board members quite well. Because we all share the same ultimate goal, these relationships have been extremely helpful in accelerating our research.
Q: Have you been personally affected by ovarian cancer?
A: My best friend’s mother died from ovarian cancer when I was in graduate school. I knew her very well, and it was so tragic to watch her decline. Her favorite oncologist was at Yale, so she would come and stay in my apartment a few times each year for medical appointments. I saw firsthand, this formidable and very stoic Russian woman reduced to almost half of her original weight as the disease progressed and as the nausea from chemotherapy took away her appetite. Sadly, her story like those of so many other women with ovarian cancer, started with vague abdominal symptoms that only lead to a diagnosis after several months, by which time the disease had already spread throughout her abdomen.
Q: What do you do when you are not working?
A: I have two young children, ages 4 and 7. When I am not working, I am enjoying my time with them, whether it’s riding bikes on our street or taking them to skating lessons. As any parent with kids of this age will tell you, half of our weekends are spent at birthday parties!
Q: Where is the last interesting place that you visited?
A: Last year we visited the Thar Desert in India where we camped overnight and rode camels before dawn to get to a vantage point from where we could see the sun rise over the dunes. It wasn’t an easy trip to do with young children, but we will never forget it.