Charles M. Perou, PhD :: Profile
Assoc. Professor of Genetics & Pathology
Carolina Center for Genome Sciences
University of North Carolina
Chapel Hill, North Carolina
Q: Tell us about yourself as a scientist and how you became interested in breast cancer research. Did you ever seriously consider another kind of career than that of the sciences?
A: I always knew that I had an interest in medicine and human disease. Shortly after college, I was extremely fortunate and got great bench experience as a research technician in the lab of Dr. Fuyuhiko Tamanoi, who was then at the University of Chicago. Through this experience, I realized that research was what I loved to do. I get great satisfaction from learning about science, and I love being the one doing the science and making the new discoveries.
My interest in breast cancer research came after my PhD work. About that time, the technology of DNA microarrays and the study of genomics were just becoming available. We thought that breast cancer, which had known different subtypes and responses to therapy, would be an appropriate field of study to apply these resources.
Today, I consider myself a translational researcher because I "live" in both the basic science and the clinical research worlds. The challenges I face are learning the in's and out's of both fields in order to translate what I've learned at the laboratory bench into the clinical setting for patients.
Q: Briefly describe your BCRF-funded research project. What are some laboratory and/or clinical experiences that inspired your work? What are your primary goals for this research?
A: My BCRF-funded research is focused on identifying the genetic and genomic causes of a subtype of breast cancer called "luminal B." Luminal B is an estrogen receptor-positive (ER+) subtype of breast cancer that portends a poor prognosis, because these patients, although they are ER+, do not benefit from much from hormone therapy or even chemotherapy. Therefore, we very much want to identify the genetic causes and to develop the appropriate treatment.
However, as is often the case in research, other findings pop up. Through our work on luminal B, we have identified yet another potential subtype of breast cancer called "Claudin-low," which appears to have many features associated with stem cells or tumor-initiating cells. Understanding the bigger picture of the relationship between cancer stem cells, tumor biology, and their response to therapy has now evolved to be our area of focus.
Q: What are some scientific developments and/or technologies that have made your work possible? What additional advances can help to enhance your progress?
A: As I alluded to earlier, one of the developments that brought me to cancer research was the DNA microarray technology. In 1997, I went to Stanford as a post-doc to study with Drs. David Botstein and Pat Brown, who were pioneers of this technology and among the first scientists to apply it to cancer.
DNA microarrays were an important advance for all of biomedical research, not just for cancer. It is one of the most commonly and widely used tools in science today. This technology has allowed us to determine whether a gene is "on" or "off" - 20,000 genes at a time. Before DNA microarray, we had to make this evaluation one gene at a time. Now, we have the capability to look at everything at once and find patterns and groups of samples that were not so obvious with earlier techniques. It's like lighting up the entire playing field at a ballpark, rather than just one section at a time. Having the ability to identify all the mutations that are present in a given patient's tumor, which is the next generation of genomic information we will gather, gives us extremely powerful information that can help to guide individualized courses of treatment, rather than a "one size fits all" approach.
Today, there is a similar revolution going on with sequencing-based technologies. Spurred on by the desire to sequence the human genome, advances in sequencing happened very quickly. Sequencing the human genome had originally taken five years and cost $1 billion, but now it can potentially be done in one week for $50,000. In addition to the increased speed, we now can also sequence more pieces of DNA at a time with the same or better precision than ever before. I think one of the future phases for breast cancer research will be applying this new technology to re-sequence breast cancer patients' tumor genomes entirely, as well as the genomes of their normal cells, to find all the variances that are present in the individual.
Our BCRF project is moving in the direction of sequencing technologies as well. I am using both microarrays and sequencing technologies, which creates twice as much work but gives us even more information. It is tough to choose one technology over another, especially because DNA microarrays are still a very good technology and we have collected data on 1,000 patients along with their treatment and follow-up histories using it. With the new sequencing technology, we have collected data from 50 patients, so it will take a while to build up the new data type to the point where we could use it to find important correlations between genetic features and patient outcomes. It is my hope and expectation that by collecting additional data, we will gain more insights.
Q: What direction(s)/trends do you see emerging in breast cancer research in the next 10 years?
A: I think over the next 10 years, with all of these new genetic and genomic technologies, we will be able to determine all of the genetic changes that occur in a patient's tumor. Combining the information we already have with additional research focused on getting new insights on all of the mutations that occur in a tumor, we will be able to "personalize medicine." By this I mean tailoring the therapeutic strategies to individual patients based on his/her genetic make-up. That specificity is going to improve patient outcomes greatly.
Q: How close are we to preventing and curing all forms of breast cancer?
A: I think we have made great progress but we do have a way to go, particularly for metastatic disease. Over the past 10 years, we have made strides. Breast cancer mortality rates are declining and have been for a few years now. But I think we will be able to make better progress now, as we now know that breast cancer is not one single disease, but at least five. Therefore, we will need to use multiple therapeutic strategies and develop additional ones to improve clinical outcomes. From a prevention perspective, we also need multiple prevention strategies to stop breast cancer recurrence and metastasis.
Q: Much has been accomplished but more needs to be done to eradicate and ultimately prevent breast cancer altogether. What is stopping us from reaching that goal?
A: This is a tough question. In some ways, I don't think anything is stopping us. This work just takes time. From my experience, I have learned that it is much easier to make a biological discovery than it is to translate that finding into a therapeutic for patients. When we finally make that translation, we then face the challenge of designing appropriate trials for patients. We need to be extremely careful with this process. After that, it takes time to recruit all of the participants you need for a clinical trial. This is why I very much encourage every breast cancer patient to try and get into clinical trials, because it is in the clinical trial phase when "the rubber hits the road." The clinical trial is the phase when we can figure out if this new drug, or this new biomarker, is actually better than what we already have. And we have to do this step. I think this is the most important part of the whole translational research process.
Q: In your opinion, how has BCRF impacted breast cancer research?
A: BCRF has facilitated creativity and innovation. I can honestly say that many of the investigations that I have used BCRF funding for were sometimes, for a lack of better words, "too creative" for conventional grant-making organizations. Some of these inquiries were ahead of their time, yet many of them have become very fruitful and important findings.
My work on the Claudin-low subtype is a good example. These findings are still controversial; many people question the significance and relevance of the Claudin-low group. However, what these people are saying about our newest subtype is exactly what they had said about the basal-like, or triple-negative, breast cancers 10 years ago. Now, triple-negative breast cancer is commonly accepted as one of the forms of breast cancer. In fact, this year's Breast Cancer Symposium hosted by the American Society of Clinical Oncology featured an entire session devoted to the topic. Interestingly, BCRF helped to support some of the research on triple-negative cancers 7 years ago!
BCRF fosters creativity and innovation by allowing us to work on lines of inquiry that other granting mechanisms may find too risky. That, I think, is the organization's biggest impact on breast cancer research.
Read more about Dr. Perou's current research project funded by BCRF.