As a chemist concerned with hard-to-cure diseases, he spent 20 years at GlaxoSmithKline (GSK), eventually working his way up to Worldwide Vice President of Discovery Medicinal Chemistry.
“When I finished up at Carolina, I felt that instead of going into academics, I’d go into the pharmaceutical industry because it’s always been important to me that I can see the impact of what I’m doing, that the things I do interface with the world,” said Frye.
Times changed, and so did the industry. Frye wondered if the future of drug discovery wasn’t in his chosen path in industry, but in the academic one he left behind. With collaborative basic science coming from every corner of campus, he felt that Carolina could be in the perfect position to make a big impact with translational medicine.
Carolina, it turns out, was interested in the same thing.
In 2007, the Eshelman School of Pharmacy and the UNC Lineberger Comprehensive Cancer Center brought Frye back to Carolina to create the Center for Integrative Chemical Biology and Drug Discovery.
The center was established to take the basic biological discoveries made by scientists who research different diseases and translate those findings into the small-molecule drugs that interact with cellular targets and improve outcomes for people.
At GSK, Frye avidly read basic science papers from academics and even worked with them from time to time. At Carolina, he works side-by-side with them.
This past spring, the center moved its operations into the brand-new Marsico Hall, a state-of-the-art research facility meant to make this kind of collaboration even easier.
“The main thing that I can do here at UNC that I could not do at GSK is to work on a day-to-day basis with physician scientists who see patients, who have an idea that they want to test for a way to treat that patient’s disease,” he said.
Locks and keys
Carolina’s biologists come to Frye with a lock – a biological state that, if it could be changed, would have a beneficial outcome for the patient.
The chemists – Frye and his researchers – look for the key: the small-molecule drug with the right properties to get into a cell and alter its function in a therapeutically beneficial way.
“At the center, the biologist presents a problem and the chemist is the one who has to solve it,” Frye explained. “Can you get a small molecule that’s safe and effective, that can be used in humans, that will modulate the target’s activity, to open the lock?”
Six years ago, shortly after the center opened, Shelley Earp came to Frye with his lock. The professor of medicine was, at the time, head of UNC Lineberger.
“We’d seen something in our biological research that, if we could inhibit it, might be able to treat different kinds of cancers,” Earp said.
Frye’s lab got to work on the keys. The two scientists’ groups met once a month for years, sharing what they’d seen in their own research to get closer and closer to the chemical interaction that would inhibit the target in cells.
The chemists on the project designed and synthesized more than 1,000 different small molecules that were tested at the center, in the Earp lab and in the lab of Doug Graham, a former Earp student and a collaborator at the University of Colorado, Denver.
They found what they needed: potent, metabolically stable and cell permeable inhibitors of Mer tyrosine kinase, which plays a specific role in certain kinds of cancer cells, increasing a tumor’s ability to survive and avoid clearance by the immune system.
One of those cancers is acute lymphoblastic leukemia, a common cancer in children. About 85 percent of children are cured with chemotherapy, said Frye, but they inevitably have lifelong neurological and cardiovascular damage from the chemotherapy.
“One of our beliefs is that we will significantly lower the dose of chemotherapy and still maintain cures for children, and they will have a normal lifespan and health status,” said Frye. “That’s the hope.”
From lab to clinic
Bringing about a desired response is easier in a test tube than in a living thing, said Earp.
“We needed to inhibit the protein inside a cell first and then see if we could do that in an animal, like a mouse,” he explained.
To explore the activity of a novel small molecule in humans requires regulatory oversight by the Food and Drug Administration, the development of a “candidate” (a robust and reproducible synthesis of the potential drug), extensive toxicology studies and the filing of an Investigational New Drug (IND) application.
All that takes money, the type of funding that doesn’t come with traditional grants, said Earp.
“We could license the idea and the candidate to a drug company for development, or we could form a startup here at UNC,” he said. “The latter would allow us to be more involved with the process, so that’s what we did with the help of Don Rose and Carolina Kickstart.”
In 2013, Frye, Earp and Graham founded Meryx Inc. to develop the Mer tyrosine kinase inhibitor they discovered in the lab into a therapeutic drug used to help treat critically ill patients. So far, the results are good in mice, rats and dogs, said Frye.
“We’ve got the compounds, and we’re at the point where we need to raise additional money to get the compound into clinical trials,” he said. “If things go well, we’ll have an IND next May or June and a clinical trial here at UNC in adults and children with leukemia.”
To find the right key for a lock, you need to commit long-term, said Frye, which is something that can go by the wayside in the pharmaceutical industry.
“If you’re focused on next quarter’s sales figures, research becomes an expense center. What I do this quarter will not affect the sales this quarter, it will affect the sales 15 years down the road,” said Frye.
“The culture of the pharmaceutical industry has changed so that it’s hard to maintain the focus for the time it takes to be successful. The only way you’re going to be successful is to have a long-term view and create an environment in which people can do outstanding collaborative science.”
Finding the right mix
Frye is eager to see Earp’s many decades of research translated into the clinic. He’s cautiously optimistic, but he doesn’t want to count chickens before they hatch.
“I’m certainly proud of the people I work with and what we’ve been able to accomplish, but right now, I’m hopeful,” said Frye. “When I see the results of the clinical trial, I’ll be proud.”
Drug discovery can take 10 to 15 years. Often, what keeps that momentum going, Frye said, is a successful relationship. With the juxtaposition of biology and chemistry so essential to drug discovery, it helps if the biologist and chemist get along.
“I’ve been lucky enough to have been involved in a number of projects that have resulted in FDA-approved medicines, and in every example there were key chemists and biologists who were champions for the target and drove the concept forward,” he said. “Shelley, Doug and I have built that type of partnership.”
Earp said that, by nature, biologists are explorers, often spending whatever time is necessary to follow a path to its conclusion. When Frye came back to Carolina, he brought not only his vision, but also a devotion to project deliverables.
“If you’re going to work with someone for years on such a long collaboration, it helps to have the same values, the same excitement and willingness,” said Earp. “The great thing about Stephen is that he also has tremendous organization skills that keep us on task.”
Twenty years in the pharmaceutical industry have shown Frye what works best. When the scientific and personal relationships click, a long-term research effort can thrive.
“One of the really important things is that you like and enjoy the people you work with, just like every other endeavor,” he said. “Shelley and I have built a strong relationship. He’s a great scientist and we’re going to make this work partly because of that relationship.”
Hazel Nichols leading study of breast cancer chemoprevention use and adherence in a large integrated healthcare setting
Approximately 1 in 8 women will develop breast cancer during their lifetime, and breast cancer remains the 2nd leading cause of cancer death among women. In 2013, the USPSTF, ASCO and NCCN published guidelines for risk reduction of primary breast cancer that encourage clinicians to counsel women about pharmacologic breast cancer risk reduction. To date, there has been no large study of chemoprevention use outside of a trial setting to evaluate risk-benefit profiles or quantify discontinuation and adherence. This study leverages the large number of Kaiser Permanente Northern California enrollees with extensive electronic pharmacy and medical record information to conduct a pilot study of breast cancer chemoprevention use. With support from a HMO Cancer Research Network Pilot Grant and a UNC Lineberger Developmental Award, Dr. Nichols and her team will validate breast cancer chemoprevention as the primary indication for therapy in a sample of 500 women; collect preliminary data on discontinuation and adherence, and estimate the level of evidence for a net benefit of chemoprevention. This work will demonstrate the feasibility of conducting a cohort study within a large integrated healthcare plan to evaluate breast cancer chemoprevention in real-world settings.
Hosted by the Kingdom of Saudi Arabia Ministry of National Guard Health Affairs, the conference is held annually in support of breast cancer awareness month to promote health education be providing details on standard of care in the management of different stages of breast cancer.
“Viruses cause 20 to 25 percent of the world’s cancers and this grant will address virally-related cancers in Malawi,” said Blossom Damania, PhD, co-director of UNC Lineberger’s Global Oncology program and assistant dean for research with the UNC School of Medicine.
Funded from a newly established NCI grant program, the award will fund the UNC-Malawi Cancer Consortium, a collaborative effort aimed at expanding current efforts in Malawi to address a growing cancer burden. UNC-Chapel Hill is one of only eight institutions in the country to receive this award.
HIV and AIDS-associated cancers present treatment challenges for physicians and a serious public health problem in nations with a high incidence of these cancers. Cancers initiated by viruses such as KSHV, EBV and HPV include Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical cancer. All are more prevalent in individuals with HIV and AIDS.
“While this award is specifically focused on HIV-associated cancers, we anticipate that it will have major catalytic effects on the national cancer control agenda in Malawi, given extremely scarce resources currently to deal with this urgent public health problem,” said Satish Gopal, MD, MPH, director of the UNC Project-Malawi cancer program.
This collaboration will begin an ambitious national effort to track epidemiologic relationships between HIV and incidence of lymphoma and Kaposi’s sarcoma in Malawi, in the current era of antiretroviral therapy (ART) scale-up. It will also study the clinical and molecular characteristics of these two diseases with the aim of developing more effective therapy. The grant is based at the UNC Project-Malawi directed by Mina Hosseinipour and Irving Hoffman, the long-term UNC clinical research program established in Malawi in the 1990s.
“Working with existing NIH research training infrastructure, we will be collaborating hand-in-hand with partners throughout Malawi to conduct much-needed research to address this growing, global health concern while also fostering the academic careers of our Malawian collaborators and investigators,” said Damania.
The grant will be led by three investigators - UNC Lineberger members Satish Gopal, Blossom Damania and Sam Phiri, PhD, MSc, executive director of Lighthouse Trust, the largest ART program in Malawi. Other key UNC faculty involved in this work are Dirk Dittmer, PhD, Mina Hosseinipour, MD, Irving Hoffman, PA, MPH, Andy Olshan, PhD, Yuri Fedoriw, MD, and Kristy Richards, MD, PhD.
The newly established cancer consortium will build upon a long-standing collaboration between UNC’s Division of Infectious Disease and Malawi’s Ministry of Health. Originally founded to help fight the HIV epidemic, this partnership has expanded to include the provision of cancer care working side-by-side with Malawian partners at one of two national teaching hospitals.
“This multidisciplinary consortium will develop capacity and conduct high-impact research focused on HIV-associated cancers that will lead into improved quality cancer care in Malawi,” said Phiri. “This will build on longstanding collaborations between the University of North Carolina at Chapel Hill, Lighthouse Trust, Malawi Ministry of Health, and University of Malawi College of Medicine.”
In 2011, UNC opened a pathology lab in Kamuzu Central Hospital, making it only the second pathology lab in the entire country. Employing telepathology using digital microscopy, the pathologists in Malawi consult with counterparts at UNC in real-time on a weekly basis. The lab, which has received a 4-star status from the World Health Organization, also provides training and research opportunities for young Malawian health professionals with an interest in cancer.
Essential partners for this undertaking include UNC Project-Malawi, the longstanding clinical research site of UNC-CH; the Malawi Ministry of Health (MOH); Lighthouse Trust; Kamuzu Central Hospital (KCH); and University of Malawi College of Medicine (COM) and the NCI AIDS Malignancy Consortium clinical trials cooperative. The UNC-Malawi Cancer Consortium is supported by the University of North Carolina at Chapel Hill through UNC Lineberger Comprehensive Cancer Center (LCCC), the Institute for Global Health and Infectious Diseases (IGHID), and the UNC Center for AIDS Research (CFAR).
During the month of October, SOCCER.COM is donating 10% of the proceeds from the sale of pink soccer gear to UNC Lineberger Comprehensive Cancer Center. In addition, special “pink” shirts are available online for $17.99 and $24.99 with 100% of the proceeds benefitting breast cancer research at UNC Lineberger!
Twelve-year-old soccer player and cancer survivor, Makaylyn Serrano, recently enjoyed a tour of Soccer.com headquarters. The people at Soccer.com arranged an amazing afternoon for the Serrano family. They presented Makaylyn with some fabulous soccer gear including a pair of cleats custom painted for her by Kickasso Kustom Sneakers.
See video from Makaylyn’s visit and purchase your pink gear at SOCCER.COM.
UNC Lineberger is grateful the support of Soccer.com and hopes to see lots of pink out on the field!
CHAPEL HILL, NC – UNC School of Medicine researchers have pinpointed a set of intriguing characteristics in a previously unknown subpopulation of melanoma cancer cells in blood vessels of tumors. These cells, which mimic non-cancerous endothelial cells that normally populate blood vessels in tumors, could provide researchers with another target for cancer therapies.
The research, published today in the journal Nature Communications, provides evidence for how these particular melanoma cells help tumors resist drugs designed to block blood vessel formation.
"For a long time the hope has been that anti-angiogenic therapies would starve tumors of the nutrients they need to thrive, but these drugs haven't worked as well as we all had hoped," said Andrew C. Dudley, PhD, assistant professor in the Department of Cell Biology and Physiology, member of the UNC Lineberger Comprehensive Cancer Center, and senior author of the paper. "There are likely several reasons why these drugs haven't been effective; our research suggests that these previously uncharacterized cells could be one of the reasons."
Most of the drugs developed to disrupt tumor blood vessels target a protein called vascular endothelial growth factor, or VEGF, which is part of a major signaling pathway in the noncancerous endothelial cells that typically line blood vessels in tumors. But other research has suggested that tumors are able to resist anti-angiogenic therapies – particularly those targeting VEGF – through a variety of complex mechanisms. In one set of experiments, Dudley and graduate student James Dunleavey, used a known anti-angiogenic drug which blocks VEGF and found that this new subpopulation of melanoma cells was more prevalent in drug-resistant tumors in mouse tumor models. Moreover, tumors composed entirely by this new subpopulation in mouse models did not respond at all to anti-VEGF therapy.
This research further elucidates the complex nature of human tumors, which are not comprised solely of the same type of cancer cell but instead feature a mixed population of different cell types with different functions.
To make these discoveries, Dunleavey first isolated what he thought were noncancerous endothelial cells from melanoma tumors. Then he conducted a genetic analysis to reveal that these cells did not express most of the well-known biomarkers common to endothelial cells. For instance, the cells didn't express VEGF receptors. This could explain why the anti-VEGF therapy was ineffective at blocking tumor growth.
"These cells looked very different from normal endothelial cells in cultures," said Dudley, who is also a member of the UNC McAllister Heart Institute. "We didn't know what these cells were. For a while, we kind of scratched our heads until Jim conducted more experiments over the course of a year to find that these cells had several markers similar to melanoma cells." Further analysis revealed that these cells were in fact a new kind of melanoma cell, one that expressed a particular protein called PECAM1, which is very important to the function of endothelial cells.
PECAM1 is an adhesion molecule. Scientists have known that endothelial cells use it to stick together to form blood vessels. When Dudley's team looked at blood vessels in tumors made of PECAM1-positive tumors, they found melanoma cells alongside noncancerous endothelial cells on the inside of vessels. "We don't think these new melanoma cells are just passively filling in gaps between endothelial cells in the tumor vasculature," Dudley said. "How they come to form blood-filled channels seems to be an active process that involves PECAM1."
Dudley and Dunleavey then teamed up with other scientists, including UNC's Paul Dayton, PhD, a professor in the Department of Biomedical Engineering, member of the UNC Lineberger Comprehensive Cancer Center, and co-author on the Nature Communications paper. Dayton's lab conducted ultrasound imaging studies showing that PECAM1-positive tumor blood vessels in mice had twice the vascular density of PECAM1-negative vessels. And the blood volume of PECAM1-positive blood vessels was 4 ½ times greater than PECAM1-negative vessels. This showed the researchers that these newly discovered PECAM1-positive melanoma cells had a real effect on the function of tumor blood vessels.
Dunleavey added, "We think these cells help allow tumor cells to interact in specific ways with bona fide endothelial cells." And this interaction – plus the lack of VEGF responsiveness – could help blood vessels and blood-filled channels resist therapies designed to destroy them.
Dunleavey and Dudley said that this discovery is likely just one part of how some tumors manage to circumnavigate therapies designed to attack their blood vessels.
"Anti-angiogenic therapies are typically used in conjunction with another drug," Dunleavey said. "It could be that we'll need to develop a combination of anti-angiogenic drugs to attack the endothelial cells that form blood vessels and the tumor cells that might form blood-filled channels in tumors."
Other authors of the Nature Communications paper, include UNC graduate students Lin Xiao, David Irwin, Victoria Brings, and Sarah E. Shelton; UNC undergraduate student Joshua Thompson; lab technician Mi Mi Kim; Janiel M. Shields, PhD; David W. Ollila, MD, professor of surgery at UNC; Rolf A. Brekken, PhD, associate professor at the University of Texas Southwestern Medical Center; and Juan M. Melero-Martin, PhD, assistant professor of surgery at Harvard.
This research was funded by grants from the National Institutes of Health and the University Cancer Research Fund at UNC-Chapel Hill.
The initiative, funded by the University Cancer Research Fund (UCRF), links state cancer data and health claims data to support cancer research. Metrics of cancer incidence, mortality, and burden in North Carolina are linked with data sources at an individual and aggregate level that describe health care, economic, social, behavioral, and environmental patterns.
A powerful data source, ICISS improves cancer outcomes in North Carolina by enabling innovative research for understanding how to:
- Discover risk factors for cancer;
- Best prevent and treat cancer;
- Disseminate and implement proven prevention, early detection, and health systems changes; and
- Improve life after a cancer diagnosis.
Meyer says she hopes to build off the excellent leadership of her predecessor, William Carpenter, PhD, MHA, who started ICISS with funds from a UCRF Innovation Award. “Thanks to the work of Bill Carpenter and an amazing team of scientists, analysts and research partners, this unique multidimensional data source provides a rich, nuanced picture of the entire cancer care continuum,” says Meyer. “I hope to continue building ICISS with a focus on broader, more innovative uses and increasing multidisciplinary collaboration across the University.”
She adds, “UCRF funding enabled the infrastructure investment that makes ICISS a model program of what is possible in population health science and cancer outcomes.”
For more information, please visit iciss.unc.edu.
The symposium, entitled Patient-Centered Care: Meeting the Requirements for New or Existing Cancer Programs, brought together nationally recognized experts on cancer care to discuss practical ideas for enhancing cancer programs.
The presenters included two keynote speakers. Sylvia Hatchell shared her reflections as a coach, player and patient. Hatchell’s emphasis on the importance of exercise during treatment was inspiring to all. Nancy Davenport-Ennis, CEO and founder of the Patient Advocate Foundation discussed helping patients navigate financial barriers to cancer treatment.
Oncology health care providers – experienced as well as novice – came away from the symposium with new knowledge and fresh idea for improving cancer care. Symposium organizer, Jean Sellers, RN, MSN, administrative clinical director at UNC Lineberger says plans are already underway for the 7th Annual Coping with Cancer Symposium next year.
DeSimone’s election to Institute of Medicine represents the third time he has been named a member of a U. S. National Academy. He was elected to the National Academy of Engineering in 2005 and the National Academy of Sciences in 2012. Fewer than 20 people in history have achieved election to all three U. S. National Academies.
DeSimone is the first professor in the state of North Carolina to be named to all three U. S. National Academies.
“Dr. DeSimone is a renaissance scientist,” said Chancellor Carol L. Folt. “He was the first to successfully adapt manufacturing techniques from the computer industry to make advances in medicine, including next-generation approaches to cancer treatment and diagnosis. It’s a beautiful example of how transcending disciplines can revolutionize science and open up entirely new fields of study. We are very proud of what Dr. DeSimone and his students have accomplished. He is a gifted and talented teacher and amazing University citizen.”
“It is humbling to join such an elite group,” DeSimone said. “This is a tribute to my students at UNC-Chapel Hill and NC State whose research at the intersection of diverse fields enables us, as a team, to create significant impact in and beyond medicine.”
DeSimone, who is also the William R. Kenan, Jr. Distinguished Professor of Chemical Engineering at NC State and of Chemistry at UNC-Chapel Hill, is known for his ability to apply insights in materials science to create advances in medicine, as well as other fields. He has more than 300 publications and holds more than 180 patents, which have also led him to found multiple companies based on his work.
During his 24-year career at UNC-Chapel Hill and NC State, DeSimone has made multiple important contributions to the advancement of medicine. In the early 2000s, he developed breakthrough materials for a new, drug-eluting, bioabsorbable cardiac stent to treat heart failure which dissolves in the body once a previously clogged artery has healed and can function on its own. The stent is now being commercialized by Abbott Vascular and is available in over 60 countries.
In 2005, DeSimone and his students invented a new technology to create nano- and micro-particles called PRINT (Particle Replication In Non-wetting Templates). PRINT enables scientists to manufacture large batches of uniform particles with tailored shapes, sizes, flexibility and chemistries using tools reminiscent of the processes used to make transistors in the microelectronics industry. PRINT particles are currently being explored by DeSimone and his team for the development of next-generation vaccines including for dengue fever, influenza and certain forms of cancer.
Since PRINT particles can be loaded with active pharmaceutical agents, including chemotherapy drugs, DeSimone’s lab is also using PRINT to pursue novel cancer treatments, as well as inhalable therapeutics for multiple conditions. DeSimone founded Liquidia Technologies, Inc. in 2005 based on PRINT, and in 2012, the company announced a large, multi-year partnership with GlaxoSmithKline focused on using PRINT to develop vaccine and inhaled products for the prevention and treatment of serious health conditions.
Also in 2005, DeSimone’s team’s work led to the creation of the Carolina Center for Cancer Nanotechnology Excellence, a ten-year, almost $40 million initiative based at UNC’s Lineberger Comprehensive Cancer Center, funded by the National Cancer Institute.
ASCO Post: Having Dependent Children Motivates Parents With Advanced Cancer to Pursue More Aggressive, Life-Extending Treatments
Findings from a pilot study of 42 parents with advanced cancer indicate that parental status is an important factor in treatment decision-making. When asked how having children influences their treatment decisions, the majority of parents (64%) responded that being a parent motivates them to pursue life-extending treatments, largely out of a desire to have more time with their children. A smaller proportion of parents (15%) identified preserving parental functioning as a treatment priority, and 12% mentioned the importance of receiving treatment close to their families, vs traveling for a second opinion, or pursuing treatment that may require long hospital stays. Parenting concerns identified in this study will inform further research in this understudied patient population. The study findings were reported at the 2014 ASCO Quality Care Symposium(Abstract 65).
“Numerous psychosocial factors influence patients’ decisions about cancer treatment. It’s important for patients with dependent children to discuss their treatment priorities with their oncologist, who may not know, for example, how important it is for a patient with children to preserve their functioning at home,” said lead author Devon Check, a PhD student at the University of North Carolina, in Chapel Hill. “We hope that our study can help oncologists engage patients with children in shared decision-making and promote alignment of the treatment plan with the patients’ priorities, including family responsibilities.”
Findings from a pilot study of 42 parents with advanced cancer indicate that parental status is an important factor in treatment decision-making. When asked how having children influences their treatment decisions, the majority of parents (64 percent) responded that being a parent motivates them to pursue life-extending treatments, largely out of a desire to have more time with their children. A smaller proportion of parents (15 percent) identified preserving parental functioning as a treatment priority, and 12 percent mentioned the importance of receiving treatment close to their families, versus traveling for a second opinion, or pursuing treatment that may require long hospital stays. Parenting concerns identified in this study will inform further research in this understudied patient population.
“Numerous psychosocial factors influence patients’ decisions about cancer treatment. It’s important for patients with dependent children to discuss their treatment priorities with their oncologist, who may not know, for example, how important it is for a patient with children to preserve their functioning at home,” said lead author Devon Check, a Ph.D. student at the University of North Carolina at Chapel Hill. “We hope that our study can help oncologists engage patients with children in shared decision making and promote alignment of the treatment plan with the patients’ priorities, including family responsibilities.”
Prior studies suggested that patients with advanced cancer who are parents prefer aggressive treatments for their illness more often than patients who are not parents. The present study, which focused solely on patients with dependent children, is the first to directly ask parents if and how having children affects their treatment preferences, beyond serving as a motivator for aggressive treatment, including preferences for palliative care and hospice. It is also the first to include qualitative methods, which helped elucidate more nuanced factors influencing decision-making.
Researchers interviewed 42 patients with metastatic cancer who have children younger than 18 years. Parents had an average age of 44, and the average age of their children was 12. When queried about preferences for palliative care and hospice, 52 percent of parents indicated an interest in using hospice services. Of these parents, many recognized hospice as a supportive resource for their family. Others were specifically interested in institutional versus home hospice care, due to a desire to protect their children from the dying experience. Twenty-four percent of parents reported an interest in receiving palliative care concurrent with their cancer treatment, although several parents seemed to conflate palliative care with end-of-life care.
Although this study included patients with a range of physical functioning and a variety of cancer types, the findings may not generalize to other patient groups. But with these initial data in hand, the researchers are already planning a larger study to explore the associations between parental status, parenting concerns and medical decision-making about treatment for advanced cancer.
A new template is now available for healthcare professionals to use when providing a survivorship care plan to cancer patients following their treatment. The template was released today by the American Society of Clinical Oncology (ASCO) and was developed under the leadership of Deborah K. Mayer, PhD, RN, chair of the ASCO Survivorship Care Plan Working Group, professor in the UNC School of Nursing and director of cancer survivorship at UNC Lineberger Comprehensive Cancer Center.
Thanks to advances in prevention, early detection and treatment of cancer, there are now more than 14.5 million cancer survivors in the United States, up from just 3 million in 1971.
“As progress continues in the fight against cancer, the number of survivors continues to grow, along with the need for programs, resources and planning to help move beyond cancer diagnosis and treatment to wellness,” said Mayer. “At the end of their treatment, patients should expect to receive a survivorship care plan, but if they don’t get one, they should ask their doctor or nurse for one.”
The new template, updating a previous version ASCO developed nearly a decade ago, was published in the Journal of Oncology Practice as part of an ASCO statement on the importance of — and minimum components for — survivorship care plans.
“This cleaner, simpler form will help healthcare professionals get survivorship care plans into the hands of patients and their primary care providers,” said Mayer. In addition to Mayer, members of the ASCO Survivorship Care Plan Working Group include Lawrence N. Shulman, MD, Dana Farber Cancer Institute; Claire Snyder, PhD, Johns Hopkins School of Medicine; and Larissa Nekhlyudov, MD, MPH, Harvard Medical School.
The survivorship care plan contains important information about treatments the patient received, their need for future checkups and cancer tests, the potential long-term or late effects of the treatment they received, and ideas for ways survivors can improve their health.
The Commission on Cancer of the American College of Surgeons has endorsed ASCO’s recommendations for the minimum elements included in the new template for implementation with their Survivorship Care Plan Standard 3.3. The elements in the template were defined through a consensus process involving multi-disciplinary stakeholders, including oncology providers, social workers, survivors and primary care providers.
In 2005, the Institute of Medicine (IOM) recommended the use of survivorship care plans, but implementation has been limited in oncology practice due to several barriers, including the time-consuming process of completing the template and lack of provider reimbursement for preparation time. An IRB-approved pilot test in 11 practices demonstrated that the new template is a time-saving and useful instrument that could make it easier for providers to fulfill the IOM’s recommendations.
Appointed UNC Lineberger’s director of cancer survivorship earlier this year, Mayer leads the cancer center’s effort to enhance clinical and research initiatives for cancer survivors. Mayer, a leading expert in survivorship and oncology nursing, focuses on survivorship research and training efforts aimed at improving programs for cancer survivors in North Carolina and across the nation.
UNC Lineberger Media Contact: Katy Jones, 919-962-3405 (office), 919-883-7848 (cell) firstname.lastname@example.org
UNC School of Nursing Media Contact: Meagen Voss, 919-966-4619 (office), 919-265-3352 (cell), email@example.com
Non-Hodgkin lymphoma is the most common type of blood cancer with over 74,000 people newly diagnosed annually in the U.S., and more than one third of patients with aggressive lymphoma eventually relapse after initial chemotherapy, and the disease becomes progressively more resistant to conventional treatment. Notably, some lymphoma patients with abnormalities in a gene called Myc have very aggressive disease course, cancers resistant to standard chemotherapy, and significantly inferior survivals. New treatment paradigms are needed, possibly by targeting this unfavorable gene, directly or indirectly, to improve survival of lymphoma patients with Myc abnormalities. Although Myc is an attractive target for anticancer treatment for the reasons mentioned above, no effective treatment has been discovered to date against this gene because it has proven extremely difficult to target.
The research aims to research ways to overcome this longstanding problem by optimally targeting the communication system in the cell that is critical in controlling expression of Myc. In essence, if we can control the communication between the Myc genes and other functions of the cell, we can effectively suppress this unfavorable gene that leads to aggressive behavior and drug resistance in cancer cells. In turn, this approach could result in death of cancer cells that are dependent on the Myc gene.
Ultimately, the successful outcome of this approach will lead to improved survival of patients with cancers that are dependent on the Myc gene. This study will have a broad impact on treatment of a variety of cancer types beyond lymphoma since the Myc gene has been associated with up to 50% of all human cancers, including breast cancer, colorectal cancer, and hepatocellular carcinoma. The targeted inhibition of Myc will not only allow identification of new anti-cancer treatment against Myc-dependent cancers but may also serve to extend our understanding of the various biological functions and drug resistance related to the Myc gene in many human cancers.
You can’t survive without a liver. It detoxifies your blood and makes essential nutrients, among other vital functions. You can get by with a small fraction of your liver, but if that goes, you’re as good as dead.
This is especially bad news for over 240 million people around the world whose livers are chronically infected with hepatitis B virus (HBV). Left unchecked, the virus can lead to fatal complications like cirrhosis and liver cancer. More than 780,000 people die from HBV-related liver disease each year.
Scientists know that disease results from the way HBVinteracts with the immune system, but they don’t understand how this happens. Fortunately, UNC immunologist Lishan Su and his colleagues now have a new mouse model that lets them study exactly how HBV hijacks the immune system, and it may soon expand the number of available HBV drugs.
U.S. researchers have largely ignored HBV compared to other major blood-borne viruses, Su says. One reason is that it’s been a long time since HBV was a big problem in the United States. In the era after World War II, army scientists and civilian doctors noted higher rates of liver disease in patients after surgeries and blood transfusions. Once they learned how to detect the virus, they altered their medical protocols to dramatically decrease the risk of spreading HBV. Then, safe and effective HBV vaccines became available in the 1980s.
But these preventive measures aren’t worth much to people who are already infected with HBV. That’s why Su’s mouse model is so important for global health.
According to the World Health Organization, in many regions including China, Southeast Asia, and Sub-Saharan Africa, more than 8 percent of the population carry the virus, even though they might not show symptoms. In these regions, infection rates resist change because the virus is passed from parent to child before the child can be vaccinated. Taiwan has shown that a strategy using both the vaccine and an anti-HBV therapy could block mother-to-child transmission, but this kind of effort is costly and requires strong health-care infrastructure. Su and other researchers want to see how they can develop new and improved medicines to help people who are already infected with HBV.
To get into a cell, HBV uses certain receptors that are only in human cells. Imagine a pattern on the surface of the virus as a key that only works on a specific lock: a particular receptor on the surface of human liver cells. The virus can’t enter the cell unless it fits the lock. Su gets around this problem by transplanting newborn, immunodeficient mice with human stem cells that mature into functional liver tissue and circulating immune cells within the mouse.
The stem cells are transplanted into the mice in a manner similar to how people receive blood transfusions, just on a smaller scale: picture a single syringe of cells rather than a half-liter bag. Over time, the human stem cells differentiate, meaning they transform and mature inside the mouse to become specific functional tissues. It may sound simple, but getting to this stage of HBV research has been a dream of Su’s for 25 years.
Su grew up in China, where HBV is a major public health concern. He came to the United States for graduate studies in virology. As a postdoc, he studied hematopoietic stem cells, a cell population that can differentiate to form all the red and white blood cells that make up the circulating immune system.
While at SyStemix, a biotech company, Su and his colleagues used humanized mice to study HIV. They transplanted human hematopoietic stem cells and human thymus into mice, which became human immune systems inside the mice. “At the time, you could only humanize the immune system—and forHIV, that’s all you need,” Su says.
In contrast to HIV, a mouse model of viral hepatitis must have human immune cells and human liver cells. Su left SyStemix to join UNC in 1996. He focused on developing humanized mice and other models to study HIV and immunity, but for the last 10 years, his lab has been working on hepatitis viruses and the liver.
The lab started moving towards the HBV model when they took on another viral liver pathogen, hepatitis C virus (HCV).HBV and HCV both infect the liver and cause hepatitis, but the features that drugs can target—their structures and life cycles—are different. The early 2000s saw a rise in HCV among people receiving highly active anti-retroviral therapy for HIV. People with HIV were living much longer, but there was an urgent need to study HIV/HCV coinfection.
Su, along with graduate student Mike Washburn and postdoc Liguo Zhang, devised a strategy to do just that. As the lab had done with mouse models of HIV, Washburn transplanted human hematopoietic stem cells into immunodeficient mice to give them human immune systems. He also made genetic changes to the mice that allowed him to replace mouse liver cells with human liver cells. When Washburn and Zhang examined these mice two months after exposing them toHCV, they saw hallmarks that let them know they had a working model of HCV infection. Su, Washburn, and Zhang have since filed a patent for these genetically modified mice through UNC’s Office of Technology Development.
The new HBV mouse model builds on the lab’s HCV model. In the final year of the HCV project, Moses Bility joined the lab as a postdoc. He knew lots about the liver and had an idea how he might improve the HCV model. “If you open a new research field, everyone benefits,” Bility says.
Bility removed the mouse liver cells by injecting the mice with an antibody. This process is easier than breeding genetically altered mice, and anyone who studies mice can access the antibody. Bility’s liver-cell replacement method worked.
Once Bility and Su had HBV-infected mice, they could start asking the questions that are likely to lead to new HBVtherapies. How does HBV affect the immune system? Which immune cells are involved in the infection process? What kind of drug might intervene?
They found a population of immune cells that were turning healthy liver cells into scar tissue through a process called fibrosis—an early phase of cirrhosis, which renders the liver nonfunctional. The fibrosis-promoting immune cells were a kind of macrophage, a cell best known for its Pac-Man-like behavior. Macrophages gobble up pathogens and other undesirables, but they also send out signals telling other immune cells to “come join the party” or “stay home.” Immunologists call the “stay home” signal immune suppression because it blocks immune activities that would get rid of a viral infection.
The macrophage population that expanded during HBVinfection was both promoting fibrosis and sending out a “stay home” signal, which meant the macrophages were making the liver a cozy space for the virus to reside. Cells with these properties have been seen in other diseases and are called M2 macrophages. When Bility’s collaborators looked at liver biopsies from people with HBV, they also found elevated levels of M2 macrophages. Taken together, this evidence suggests that M2 macrophages are a new potential therapeutic target for disrupting HBV infection.
Su is quick to point out that people have been studying macrophages and cancer for a long time, meaning that the lessons already learned from studying M2 cells in cancer may accelerate the development of HBV therapies. Bility is now testing different drugs in his humanized mice to see which ones can reduce HBV infection.
“It’s an exciting time to be working in HBV research,” Su says. He’s looking forward to seeing where the new mouse model will lead. We don’t yet have a new anti-HBV drug, but Su’s group has reached a crucial first milestone in its effort to block HBV’s fatal impact.
Victoria Bae-Jump, MD, PhD, associate professor with the UNC Department of Obstetrics and Gynecology, served as the keynote speaker at a luncheon hosted by She ROCKS (Research, Ovarian, Cancer, Knowledge, Support) on September 19, 2014 in Wilmington, North Carolina. Dr. Bae-Jump talked about incidence, risk factors and treatments associated with one of the deadliest cancers for women – ovarian cancer. She also spoke about her research which focuses on obesity, diet and the development and progression of ovarian cancer as well as metabolic targeted therapies in the treatment of this disease.
The luncheon was hosted by ovarian cancer survivor and bank executive Beth Quinn, who leads the organization, She ROCKS. About her diagnosis Beth commented at the event, “I never went into a dark hole.” She adds. "I said ‘You know Lord, I didn't sign up for this. I don't know anything about it, but if you will walk with me, I'll do it and I'll help the very next person."
Proceeds from the luncheon were earmarked for New Hanover Regional’s Zimmer Cancer Center and Dr. Bae-Jump’s research in ovarian cancer at UNC.
Dr. Bae-Jump shares, “I feel very honored to have been at the very first She ROCKS event. Beth Quinn, her friends
and family have done an amazing job in starting She ROCKS bringing increased awareness and research dollars to combat ovarian cancer.” She adds, “The funds from She ROCKS will help accelerate our research efforts, especially those projects focused on early detection and the relationship between diet and ovarian cancer development and progression. Thank you so much Beth Quinn and she ROCKS!”
The inaugural event was such as success; Beth has already secured a bigger venue in Wilmington for next year’s event.
Guests of the luncheon were encouraged to wear teal, which is the color for ovarian cancer awareness.
Every single human cell contains every single human gene. But depending on the cell, only some of these genes need to be expressed or “turned on.” For instance, a heart cell has all the genes needed for, say, proper kidney function. But that heart cell won’t express those genes. In a heart cell, those genes are “turned off.” When one of these “wrong” genes is turned on by mistake, the result can be rampant cell growth – cancer.
How this happens used to be the stuff of science fiction. Now, scientists know that there are tiny proteins –epigenetic proteins - that sit atop the genetic code inside cells. These proteins are responsible for turning on or off the genes.
Now, UNC researchers discovered that one gene-regulating protein called Bre1 must be maintained in the proper amount for other epigenetic players to do their jobs properly. It’s a key coordinator in the sort of cellular scenes that can turn a healthy cell into a cancer cell.
Setting the scene
Within each cell of the body is an ongoing and intricate performance with genes playing some of the leading roles. As with all performances, the actors do not act alone, but instead, rely on support from behind the scenes. This supporting staff provides the script and cues for what the genes are supposed to say and do – how genes are accessed and used. Important members of the support staff are histones – the proteins that package genes inside cells and allow them to be used for various cellular functions that keep us healthy; they allow the plot to unfold perfectly.
Unfortunately, sometimes cues are missed or lines are forgotten and the show doesn’t go as planned. This causes the actors to speak when they should be quiet or stay quiet when they should speak. And if one of these actor genes happens to be essential for, say, cell growth, then the result can be disastrous. The actors take the story in an unintended direction.
All this supporting staff is part of epigenetics – epi meaning on or above – a field that focuses on the environment and the players that allow our genes to act.
“I think epigenetics is a new frontier of cancer research,” says Brian Strahl, Ph.D., a professor of biochemistry and biophysics in the UNC School of Medicine. “We can now sequence the entire genome of a cancer cell, and what we’re finding is that many cancers have mutations in the epigenetic machinery. We’re not just finding this in cancer cell lines in the lab but in cancer patients.”
The director’s cut
Strahl, who’s a member of the UNC Lineberger Comprehensive Cancer Center, said major questions surround how histones wrap up the DNA into chromatin – a structure that allows or denies access to the genetic information inside our cells.
This is what Strahl studies. His goal is to figure out precisely how histones contribute to basic biological functions and, in turn, contribute to cancers and other diseases. Adding a twist to this idea, however, is the fact that not every histone is the same.
“We’ve already learned that the histone proteins found at the sites of genes can be chemically modified with a variety of small chemical “tags” that either promote or further prevent access to our genetic information – our DNA. And this access or denial ultimately affects genes so they are either activated or not.”
These chemical tags come from a variety of sources – mainly the food we eat, the chemicals in the environment that gets inside us through our skin and lungs, for example, and the various biological chemicals that simply make us tick. Proper nutrients, for instance, allow for the formation of chemical tags to direct the histones to activate genes in the proper ways. Nasty environmental stuff, such as cigarette smoke, can mess up the epigenetic machinery.
Yet, these chemical tags are not ultimately in charge of the genes. Another layer of proteins above the histones are responsible for putting on the chemical tags.
“Something has to ensure that these chemical tags on histones are regulated properly, to ensure that the tags are only present on the right genes at the right time,” Strahl said.
Strahl and graduate student Glenn Wozniak focused on one of the proteins that add these chemical tags – a protein called Bre1, which keeps one tag – ubiquitin – in check.
In a sense, Bre1 hires ubiquitin; it allows ubiquitin to do its job.
Ubiquitin is known to help a histone open up the cell’s chromatin to expose genes for activation. When ubiquitin is finished, it is removed from the histones, and the genes become inactivated.
If this process goes awry – if the genes are allowed to remain active indefinitely – then normal cells can turn into cancer cells. And the entire cellular performance collapses.
The Goldilocks effect
Until now, how this happened was unclear. Through a series of experiments, Strahl and Wozniak found that, like the chemical tags themselves, a precise amount of Bre1 must be maintained to ensure that just the right amount of ubiquitin is added to histones.
“We found that if there’s too little Bre1, then the gene doesn’t turn on,” Strahl said. “If there’s too much, the gene doesn’t shut off. We call it the Goldilocks effect.”
Wozniak added, “We also found that when Bre1 is not needed or when it doesn’t perform its function, it’s removed as a control mechanism. There won’t be as much ubiquitin on histones because Bre1 is not there.”
Strahl and Wozniak’s finding illuminates what had been an epigenetic mystery. Scientific literature on Bre1 had been mixed.
“Some studies indicated that Bre1 had a role as a tumor suppressor,” Strahl said. “Other studies showed that it’s a cancer promoter. So there’s been conflicting evidence about all of this. Now we know. If there’s too little Bre1, the gene won’t turn on.” This could turn off the genes that protect the cell from cancer. “If there’s too much,” Strahl said. “Then the genes might not turn off.” This could also trigger cancer development.
“When you think about it, Bre1 could be a really good target for a cancer drug,” Strahl said. “Cancer cells divide rapidly. A lot of chemotherapies involve creating DNA damage within all rapidly dividing cells. But if you just target the Bre1 protein and maybe shut it off, you could have very bad outcomes specifically for rapidly dividing cancer cells. They wouldn’t be able to transcribe genes anymore.”
Strahl and Wozniak’s study appeared in the journal Genes and Development. The National Science Foundation funded this work.
UNC Lineberger members Melissa Troester, PhD, associate professor of epidemiology at the Gillings School of Global Public Health, and Liza Makowski, PhD, assistant professor of nutrition, are co-principal investigators for BCERP, a five-year initiative to study how obesity and other influences may affect susceptibility to basal-like breast cancer (an aggressive subtype). The myBCrisk website, part of the BCERP and the UNC Center for Environmental Health and Susceptibility (CEHS), was developed with help from the UNC School of Information and Library Science and community outreach partners Kathleen Gray and Neasha Graves, of the CEHS. The project is funded by the National Institute of Environmental Health Sciences, with support from the National Cancer Institute and the Avon Foundation.
The site features informational resources, a tool for assessing personal risk factors and videos of young black cancer survivors.
“It was an amazing opportunity for a bench researcher such as myself to work with outreach experts to develop this website,” Makowski said.
“The site is a valuable tool for helping women understand breast cancer risk,” added Troester.
For more information, contact Neasha Graves at firstname.lastname@example.org or (919) 966-3746.
“You don’t have the choice that you have cancer, but you have the choice in how you deal with it.” Watch Coach Sylvia
Inspiring words from UNC women’s basketball coach and cancer survivor Sylvia Hatchell, who spoke at last week’s 10th annual Fast Break Against Cancer. Hosted annually by UNC men’s basketball coach Roy Williams, the live auction breakfast event raised $213,000 for cancer research and treatment at UNC Lineberger.
Almost a year since her leukemia diagnosis in October 2013, Hatchell remarked during the event on her diagnosis, treatment and recovery, sharing photos from throughout her journey.
"I mean, I look back and I'm just like, 'Wow,' you know," Hatchell said. "When I look at that and think that I would have to go through that, I would say there's just no way. You don't realize how strong you can be until strong is all you have."
Hatchell graciously thanked UNC Lineberger and her entire care team, which included among many people, Drs. Peter Voorhees, Thomas Shea, Claudio Battaglini and Physician’s Assistant John Stader. An avid athlete prior to her diagnosis, Hatchell continued to exercise throughout her treatment with Battaglini, an associate professor of exercise and sport science, and cites that physical activity as a significant factor in her recovery.
You don't realize how strong you can be until strong is all you have." - Sylvia Hatchell
During her remarks, Hatchell also unveiled an office chair that was passed down to her from Dean Smith, announcing that she will auction off the Caroline blue chair with proceeds benefiting UNC Lineberger.
Williams also gave remarks introducing Coach Hatchell to the Smith Center floor packed with over 400 attendees.
“When you are family and you’re friends with someone that’s close who is fighting this. And when you are friends and colleagues with Sylvia Hatchell, and fighting with her and what’s she gone through with her family, it’s got to make you want to do even more.”
Williams urged the crowd to come together and do “every little thing we can do” to support cancer research. Williams clearly has done much more than a little. Over the past decade, he has raised more than $1.77 million for cancer research, treatment and prevention programs.
Following the close of the silent auction, Coach Williams and Woody Durham kicked off the live auction. Auction items included an opportunity to watch a home men’s basketball game from the team bench, a sleepover in the Smith Center, a Carolina Basketball History package featuring a UNC Basketball Hall of Fame tour led by Woody Durham, and more.
A special thanks to presenting sponsor Atlantic Packaging and to all of our generous sponsors.
“We could not invent a better person for this role,” said Lisa Carey, MD, medical director of the UNC Breast Center, division chief of hematology and oncology at the UNC School of Medicine, and physician-in-chief of the N.C. Cancer Hospital. “Matt is smart, thoughtful, a terrific doctor, and a true problem-solver, key attributes in this time of rapid change in our system and in health care in general.”
In this role, Dr. Milowsky will be responsible for the clinical policies of the nationally ranked cancer hospital, working in conjunction with clinic management to ensure the most effective, accessible and high quality care for patients.
"Dr. Milowsky’s combination of clinical acumen, patient-centered care and research expertise will assure our patients will be treated in a timely, innovative and compassionate manner,” said Shelley Earp, MD, director of UNC Cancer Care.
“I am excited to take on the role of medical director serving as both a member of the N.C. Cancer Hospital’s Executive Committee and co-chair of the Operations Committee. My goal is to work together to streamline and improve the clinical operations for our patients,” said Milowsky.
Joining UNC in 2011, Dr. Milowsky brings a passion for clinical and translational research with a strong focus on the development of clinical trials and novel treatments for patients with genitourinary cancers. Dr. Milowsky has published in peer-reviewed journals and written several book chapters. He served as an author on the Genitourinary Cancers section of the ASCO Medical Oncology Self-Evaluation Program, and recently was appointed as an associate editor for the 5th edition of the publication.
Named to “Best Doctors in America” the last two years in a row, Dr. Milowsky has received several honors and awards including the Henry Shepard Bladder Cancer Research Award and the MSKCC Paul Sherlock Housestaff Teaching Award. As an active member of the bladder cancer advocacy community, Dr. Milowsky also serves on the BCAN Scientific Advisory Board, an international group of distinguished leading academic urologists, oncologists, radiation oncologists, and pathologists working within the bladder cancer field, representing many of the major cancer centers in the U.S and Canada.
He completed a fellowship in Medical Oncology and Hematology at the New York Presbyterian Hospital (NYPH)-Weill Medical College of Cornell University. After completing his fellowship training, he remained on staff at New York Presbyterian Hospital-Cornell and focused on the treatment of patients with and research related to genitourinary malignancies. At Cornell, he became the Director of the Genitourinary Oncology Research Program. He subsequently joined the Genitourinary Oncology Service at Memorial-Sloan Kettering Cancer Center and led the translational research program related to urothelial cancers with a focus on the development of novel targeted therapies for patients with advanced bladder cancer.
Media Contact: Katy Jones, UNC Lineberger Comprehensive Cancer Center’s Director of Communications and Marketing, at email@example.com or 919-883-7848.
Pam Kohl, executive director of Komen North Carolina to the Coast said, “The grants bring Komen’s total research investment in North Carolina to nearly $31 million since 1982. Since 1997, the Affiliate has funded nearly $15 million to community health programs that provide screening, education, financial aid, and social and emotional support to women and families throughout our 29 county service area in Central and Eastern North Carolina.”
An award of $450,000 was given to Michael Emanuele, Ph.D., to apply large-scale technologies which will systematically identify proteins that are broken down and recycled by the E3 Ubiquitin protein family. Any differences that occur in cancer cells compared to normal cells will help to identify possible therapeutic targets that promote cancer growth, with a focus on finding novel therapies for triple negative breast cancer.
$200,000 in continued funding to Komen Scholar Lisa Carey, M.D. is developing a method to rapidly assess the genetic traits of the primary breast tumor and compare it to those found elsewhere in the body (metastases) in order to uncover which genetic changes occurred that resulted in the development of metastatic disease.
Continued funding of $175,000 has been awarded to Komen Scholar Claire Dees, M.D., M.Sc., will continue to build a strategic infrastructure that will encourage greater numbers of patients with metastatic breast cancer to enroll in narrowly focused Phase 1 clinical trials which will facilitate additional research into treatments for metastatic breast cancer patients and improving patient access to new drugs.
More than $50,000 in funding to Shelley Earp, M.D., to carry out Phase III of the Carolina Breast Cancer Study (CBCS) – the largest population-based study of breast cancer in African-American and Caucasian women – which will involve obtaining clinical treatment and outcomes data from this population while working with healthcare providers across North Carolina to get treatment records. The study would be the first to address how treatment decisions, access to care, and financial or geographic barriers impact breast cancer.
The Komen North Carolina Triangle to the Coast (NCTC) Affiliate serves 29 counties in central and eastern North Carolina; holding two annual Race for the Cure events in Raleigh (June 13, 2015) and Wilmington (March 7, 2015). Since its first Race in 1997, nearly $15 million has been raised and used locally for breast cancer research, education, advocacy, health services and social programs. Seventy-five percent of the net proceeds generated by the Affiliate stay in the service area. In 2014, $738,000 was granted to provide a continuum of breast health services to underinsured and uninsured women from the Triangle to the Coast.