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Cancer Survivor Becomes Ambassador for Hope

The latest installment in UNC Health Care's Real Medicine video series features Ashley Burnette, 11-year-old cancer survivor and Patient Ambassador at the North Carolina Children's Hospital.

Thursday, February 12, 2015

Hi!  My name is Ashley Burnette.  I live in Raleigh, N.C., I am 11 years old and I'm in the 6th grade. I am proud to say that I am a cancer survivor. On August 27th of 2010, I was diagnosed with Stage 4 Neuroblastoma and later was diagnosed with Non-Hodgkin’s Lymphoma.  I went through many battles that have led to me being able to say that I am CANCER FREE, but that isn't a short story to tell. I have gone through a lot to gain that title and I realize it’s a blessing that I'm able to hold that title.  My goal in life is to be someone that will make a difference in this world and someone that will be remembered for doing so.  I hope to be a role model for many kids battling cancer and to encourage all of them to keep fighting. 

When I was going through treatment, I was asked to be a Patient Ambassador for the North Carolina Children’s Hospital and I was able to share stories from my journey with lots of people.  In 2014, I was chosen to be the 2014-2015 National Youth Ambassador for Hyundai Hope On Wheels, which is one of the leading funders for pediatric cancer research in the U.S.  As their ambassador, I get to travel around the country to lots of children’s hospitals and share my message of hope to other kids and families battling cancer.  I really enjoy public speaking and hope that when other kids see how I fought a hard battle and made it through, that they too will never give up!

During my treatment, I made lots of friends who were also battling cancer.  Unfortunately more than half of those friends didn’t survive. No kid should have to go through the pain of losing one of their best friends to cancer. I felt like I lost a piece of myself when each of them passed. THEY are the reason I need to do all I can to help find a cure for this horrible disease!  My hope is that in my lifetime, no other parent will have to hear the words, “Your child has cancer.”  My plan is to do all I can to bring awareness to childhood cancer and to help raise money for research so we can end childhood cancer FOREVER!!!

Love, Ashley Burnette

Sleep for Cells

With new funding, a UNC startup is poised to halt the most devastating effects of chemotherapy.
Sleep for Cells click to enlarge Photo by Donn Young

By Susan Hardy, Endeavors

It started with a fear of planes.

“I don’t like to fly, so I’m a master at distracting myself,” saysUNC cancer researcher Ned Sharpless. He was about to head from North Carolina to California, and he needed to prep for the transcontinental flight.

“I downloaded all of Battlestar Galactica, and in one episode they’re running around looking for something for radiation poisoning. And I was like, exactly how would a radiation poisoning drug work?”

Sharpless started dreaming up a real-world version of the sci-fi drug. That has led to a technique to protect cells not just against radioactive attack, but from the far more common assault of cancer chemotherapy. Today, Sharpless’s company G1 Therapeutics has attracted $33 million in new investments to bring the treatment to cancer patients and test other drugs for cancer.

There are two ways you could combat radiation damage, Sharpless thought after that day on the plane. One way would be to make a drug that stops radiated cells from dying. He figured that would be a bad idea, because if you keep damaged cells alive, they could turn into cancer.

The other option would be to help the damaged cells repair themselves, or prevent the damage in the first place. “One trick to do that is to change where the cell is in the cell cycle, because the cycle has a profound effect on the cell’s ability to repair damage,” Sharpless says. In the life cycle of a cell, it rests, copies its DNA, rests some more, and then divides. Cells in the first resting phase, called G1, are less vulnerable than cells that are preparing to divide.

So his team’s goal became to pause healthy cells in G1, to protect people from radiation damage from a nuclear attack—or from the similarly toxic effects of chemotherapy. “Some of the best cancer drugs are still these terrible, noxious, DNA-damaging molecules discovered 50 years ago,” Sharpless says. “They are really good drugs that cure cancer when nothing else will.”

The team got the opportunity to test the idea when it was a studying a compound that blocks two enzymes, CDK 4 and 6. Drug companies were interesting in using these enzymes to stop cancer cells from dividing and multiplying, but Sharpless wondered whether they could also protect healthy cells by pausing them in the resting phase. In 2007, Sharpless’s team found that the compound protected the bone marrow of mice from radiation toxicity. In effect, it stopped the damage that, in a human receiving chemotherapy, leads to infections, anemia, and bleeding.

There’s a long road from a study result to an FDA-approved treatment—one that Sharpless almost didn’t start down. He was a researcher and a clinician, not an entrepreneur. But a Harvard colleague who was part of the research, Kwok Wong, convinced Sharpless they should start a company to move their work along to a real drug that could be used in conjunction with chemotherapy.

G1 Therapeutics, begun with a grant from the Carolina KickStart program, arrived in Research Triangle Park in 2008, just at the right moment to provide work for good scientists laid off in the economic downturn. The company worked with several scientists to make a strong CDK 4/6 inhibitor called G1T28.

The first phase of G1T28 testing, on healthy subjects, showed that the drug is nontoxic and does what it’s designed to do—pause bone-marrow cells in G1 when you give the drug through an IV. After the drug dissipates from the blood, the cells start dividing normally again.

Now, the company has announced that it attracted $33 million in new venture capital, a step that will allow it to start more clinical trials in 2015. Lung-cancer and breast-cancer patients receiving chemo will get the drug to see if it protects their marrow. By sometime in 2016, Sharpless thinks, we’ll know how well it worked.

G1 Therapeutics employs 11 people full-time at its headquarters in Research Triangle Park, and outsources more work to RTP contract research organizations. In the next phases of clinical trials and research into the tumor-suppressing abilities of CDK 4/6 inhibitors, G1 will likely expand its payroll.

“Most patients with cancer eventually get cytotoxic chemotherapy, so the need for this kind of treatment is still going to be high,” Sharpless says.

Ned Sharpless is the Wellcome Distinguished Professor in Cancer Research in the UNC School of Medicine and director of the UNC Lineberger Comprehensive Cancer Center. His initial work on CDK4/6 inhibitors was supported by the University Cancer Research Fund, an investment by the N.C. General Assembly to fund innovative research to detect, treat, and prevent cancer.

Sharpless started G1 Therapeutics with Kwok-Kin Wong, a Harvard Medical School researcher. They began the company with a grant from the N.C. Translational and Clinical Sciences Program’s Carolina KickStart program, developed to provide support for UNCfaculty in commercializing biomedical technologies through startup generation. The company was funded by the National Institutes of Health, the N.C. Biotechnology Center, and venture capital.

Tennis star Isner hosts fifth annual tennis exhibition benefiting UNC Lineberger

To give back to an institution that he credits with saving his mother’s life, America’s top-ranked men’s singles tennis player John Isner returned to his hometown of Greensboro on Saturday, February 7th for his annual tennis exhibition event.
Tennis star Isner hosts fifth annual tennis exhibition benefiting UNC Lineberger click to enlarge (L to R) UNC Lineberger member Dr. Ben Calvo, host John Isner, UNC Lineberger Director Dr. Ned Sharpless, James Blake

This was the fifth year that Isner has hosted the Ebix Charity Challenge to benefit the UNC Lineberger Comprehensive Cancer Center. Isner’s mother, Karen, was treated for colon cancer at the N.C. Cancer Hospital, UNC Lineberger’s clinical home in Chapel Hill.

“They do amazing things,” Isner said of UNC Lineberger. “They saved my mother’s life, they’ve saved so many other lives. Our family is forever in debt to them, and I’m so fortunate to have a lot, a lot of good friends come out and help.”

Isner is the top-ranked American men’s singles tennis player, and is ranked No. 18 in the world on the Association of Tennis Professionals world men’s singles rankings.

He was joined Saturday by his friend, tennis player and author James Blake, Olympic gold medalists and top-ranked doubles players Bob and Mike Bryan, and tennis coach Wayne Bryan, the Bryan brothers’ father who also served as emcee of the event.

Karen’s surgeon Dr. Ben Calvo, director of the UNC Gastrointestinal Multidisciplinary Oncology Program, spoke at the event, along with UNC Lineberger Director Dr. Norman Sharpless.

The challenge featured a youth tennis clinic at the Piedmont Indoor Tennis Center, a pre-match reception at the University of North Carolina at Greensboro Alumni House, and exhibition tennis matches. A VIP autograph reception rounded out the day’s events.

The challenge has raised significant funds for UNC Lineberger to date. Isner continues his fundraising efforts for the cancer center through a Crowdrise web site. For more information, please visit https://www.crowdrise.com/johnisner

Smith awarded funding to identify research topics that matter most to patients

To identify important medical questions that haven’t been fully answered by researchers yet, doctor and researcher Angela Smith is turning to patients for guidance.
Smith awarded funding to identify research topics that matter most to patients click to enlarge Angela Smith, MD, MS

Smith, MD, MS, assistant professor of urology at the University of North Carolina School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center, is working on a project that will uncover top questions that patients have about bladder cancer.

“While medical researchers might intend to positively impact patients through their research, the questions they’re asking may not be the ones most important to patients,” Smith said. “We want to get a better idea of the research questions that matter most to patients.”

Toward that end, Smith has been awarded a $121,237 contract by the Patient-Centered Outcomes Research Institute (PCORI). The Eugene Washington PCORI Engagement Award will support a two-year effort to survey willing patients from a more than 4,000-person online community. The online community, which involves patients, caregivers, and others, is part of the Bladder Cancer Advocacy Network, a national advocacy group that supports bladder cancer research and patients.

Smith said she chose to focus on bladder cancer because more active research is needed. It’s the sixth most common type of cancer in the United States, and has a five-year survival rate of 77 percent.  Invasive bladder cancer can mean a life-changing surgery to remove a patient’s bladder.

By working through the Bladder Cancer Advocacy Network online community, Smith will poll a representative sample of the U.S. bladder cancer population to find out what the most important questions are. She thinks the project is a good way to go about identifying questions, rather than relying on doctors in the clinic.

From time to time in her own practice, patients have asked questions that have no evidence-based answers, and current research is not addressing many of them. They’ve ranged anywhere from “why does my sense of taste change after surgery?” to more complex questions about treatments.

“We can’t rely solely on clinicians to ask patients which research questions matter – they are focused on explaining the disease, diagnostic options and treatment options,” she said. “And patients are not necessarily in the right mindset to discuss research questions at the time of diagnosis and in the midst of treatment. I think sometimes the best time is after patients have been diagnosed, after they’ve been treated, at which point they can think to themselves, ‘I wish I had more evidence here to guide my decision.’ ”

To pick the top questions, Smith said she plans to have a group prioritize questions. This group will include patients, caregivers, nurses, doctors, researchers, payers, and policy-makers, so that all viewpoints will be represented. They then plan to send the list of prioritized questions to funding organizations and researchers to help guide their work. They also plan to set up the infrastructure to be able to systematically poll patients in the future.

Smith has already been involved in trying to identify research that matters to patients as a member of a Patient-Centered Outcomes Research Institute advisory panel. She said the work opened her eyes to the fact that researchers can sometimes have “blinders on” in terms of what they think is important.

And through her work on this project as well as in her medical practice, Smith has a desire to uplift people. She said that has been with her since she was a child. In her grandmother’s salon as a young girl, she worked odd jobs sweeping up and taking out customers’ curlers. She enjoyed developing relationships with customers, and seeing how their experience in the salon could transform them.

“When they left the salon, they were always happy due to the attention given not only their styling but any burden they brought for discussion – and that’s a quality of life experience,” Smith said. “That’s not medicine of course, but there’s no reason you can’t apply the same principles to it. Your job as a physician, as a surgeon, is to explain the diagnostic and treatment options for your patients, but to be attentive to any question – no matter how seemingly minor – and to set them back out into the world confidently, their stresses perhaps not fully resolved, but at least manageable.”

Her project is part of a portfolio of projects approved for PCORI funding to help patients and other health care stakeholders become actively involved in health research, according to a PCORI news release. In total, PCORI has awarded more than $3 million to support 18 projects to-date through this award program so far. For more information, visit their website.

PCORI is an independent nonprofit authorized by Congress in 2010 to fund comparative effectiveness research that will provide patients, their caregivers, and clinicians with the evidence needed to make better-informed health and health care decisions.

A soft hat – and a tender heart

Most 12 year olds collect Pokemon or baseball cards. But, for 7th grader Gray Garber, it’s hats. And not just any hats. Hats that are fun, happy and perfectly soft on the inside – soft enough for the delicate heads of pediatric cancer patients at the N.C. Cancer Hospital.
A soft hat – and a tender heart click to enlarge Gray Garber spent the last year gathering 75 hats for Kaps for Kids.
A soft hat – and a tender heart click to enlarge Garber presents the hats to UNC urologic oncology nurse practitioner Mary Dunn

Gray Garber started collecting hats for the NC Triangle Oncology Nursing Society’s (NC TONS) Kaps for Kids program three years ago when Katy Lynn Garber, Gray’s mom and medication assistance coordinator at UNC Health Care, brought home a flier about the new program from a co-worker.

“I brought home the flier and Gray picked it up and asked ‘What’s this?’”

That question spurred a conversation between Garber and her son – 9 at the time – about cancer, its impacts on patients and the discomfort that hair loss triggered by chemotherapy may cause a patient on a cold, wintry day.

That conversation inspired Gray. The first year he shopped for a few hats for the program. The following year, he collected around 12. This past year, that number spiked to 75.

“He just shopped for hats throughout the year and stashed them away in his closet,” said Garber. “I was shocked when we pulled them out to turn them into Kaps for Kids at how many he had gathered throughout the year. He was on a mission.”

As he shops throughout the year, Gray takes the hat selection process very seriously.

“I open every single hat I buy and check to make sure it is soft enough,” says Gray. “If it’s not, it goes back to store.”

The hats also need to be “fun and happy,” says Gray. “The best one I ever got was in the shape of a hot cocoa cup. That one was pretty cool.”

The Kaps for Kids program was started by UNC urologic oncology nurse practitioner Mary Dunn, who also serves as community outreach coordinator for NCTONS. Founded in 2011, the initiative collects hats and divides the donations between the UNC and Duke pediatric oncology programs. Last year, she collected nearly 1,300 hats and is aiming for a similar number this year.

“I have received hats from all over the state.  You can feel the love and care that has gone into these hats. Gray’s contribution to our program is so heart-felt and invaluable to our patients.”

When asked what motivated him to start collecting hats, Gray simply states, “Because you have to help give to other people.”

“He is the most tender-hearted child,” said Garber. “He is always looking for ways to help other people.”

Gray’s goal for next year?  100.

For more information on the Kaps for Kids program,
please contact Mary Dunn at .
New hats are appreciated for children of all ages.

UNC-Chapel Hill spinout secures $33 million investment to advance novel cancer treatments

One of nation’s top universities yields more than 150 startup companies to date, including G1 Therapeutics, creating jobs and advancing innovation and entrepreneurship.
UNC-Chapel Hill spinout secures $33 million investment to advance novel cancer treatments click to enlarge Norman Sharpless, MD

An RTP-based pharmaceutical company with roots at the University of North Carolina at Chapel Hill has received $33 million in Series B venture capital funding to develop more effective and less toxic methods to treat patients with cancer. 

G1 Therapeutics (G1), a company based on discoveries made at the UNC Lineberger Comprehensive Cancer Center, will use the new financing to accelerate clinical development of its lead CDK4/6 inhibitor for antineoplastic and chemoprotection indications.

“G1 Therapeutics’ success reflects Carolina’s mission to spur innovation and entrepreneurship by our faculty and students,” said Judith Cone, the Chancellor’s Special Assistant for Innovation and Entrepreneurship and UNC’s Interim Vice Chancellor for Commercialization and Economic Development. “To date that effort has yielded over 150 startup companies that employ more than 8,000 people in North Carolina.  More than 60 of those companies were – like G1 Therapeutics – created to license technologies developed here at UNC-Chapel Hill.”

The Series B syndicate is led by Eshelman Ventures and RA Capital Management, who are joined by new investors Lumira Capital and Boxer Capital of Tavistock Life Sciences, as well as the company’s existing investors Hatteras Venture Partners, MedImmune Ventures and Mountain Group Capital. Fred Eshelman of Eshelman Ventures and Peter Kolchinsky of RA Capital will join the G1 Board of Directors.

G1 originally began in 2008, then known as G-Zero, with help from Carolina Kickstart, a UNC-Chapel Hill program that works to turn university research into new companies, based on discoveries made by UNC Lineberger Director Norman Sharpless, and Kwok Wong, director of the Belfer Institute for Applied Cancer Science at Harvard Medical School. In 2012, the company changed its name to G1 Therapeutics, after receiving seed-financing from Hatteras Venture Partners. 

In 2014, the company opened a clinical trial to test the safety of a novel drug that causes certain groups of bone marrow cells to temporarily stop dividing—camouflaging them from chemotherapy. The drug, called G1T28, is currently being tested in healthy volunteers with the next phase of trials in cancer patients expected to begin in 2015.

“G1 Therapeutics’ success reflects the critical role university research plays in economic development,” said Barbara Entwisle, UNC’s Vice Chancellor for Research.  “UNC-Chapel Hill is one of the nation’s top-ranked universities, conducting more than $800 million worth of sponsored research each year.  New companies like G1 are just one example of the way that work pays off for our state.” 

The preliminary research which led to the founding of G1 was supported by the University Cancer Research Fund, a landmark state investment in cancer research at Carolina. Further development of G1 was supported by National Institutes of Health commercialization grants.

Editor’s Note: Information about businesses that have emerged from UNC-Chapel Hill and UNC Research can be found here.

About G1 Therapeutics, Inc.

G1 Therapeutics, Inc. is a privately held clinical-stage pharmaceutical company based in Research Triangle Park, N.C. that focuses on the discovery and development of novel small-molecule therapies to address significant unmet needs in oncology. The company is leveraging its proprietary kinase drug discovery platform to advance a pipeline of first-in-class compounds and best-in-class drug candidates that address two markets: CDK4/6 antineoplastics and protection of the bone marrow from damage by chemotherapy (chemoprotection). The company’s lead program, G1T28, is a highly potent and selective CDK4/6 inhibitor that is currently being evaluated in Phase 1a clinical trials. Visit www.g1therapeutics.com for more information.

Potential pancreatic cancer treatment could increase life expectancy

Device that drives drugs into solid tumors that are poorly vascularized opens the possibility of life-saving surgeries in cancer patients.

Pancreatic cancer cells are notorious for being protected by a fortress of tissue, making it difficult to deliver drugs to either shrink the tumor or stop its growth. Now researchers at the University of North Carolina at Chapel Hill have developed a device that could change all that: By using electric fields, the device can drive chemotherapy drugs directly into tumors, preventing their growth and in some cases, shrinking them. 

The work, published Feb. 4 in Science Translational Medicine, opens the possibility of dramatically increasing the number of people who are eligible for life-saving surgeries. It represents a fundamentally new treatment approach for pancreatic cancer, which has a 75 percent mortality rate within a year of diagnosis - a statistic that has not changed in more than 40 years. 

“Surgery to remove a tumor currently provides the best chance to cure pancreatic cancer,” said Joseph DeSimone, who is Chancellor’s Eminent Professor of Chemistry at UNC and William R. Kenan, Jr. Distinguished Professor of Chemical Engineering at NC State University. “However, often a diagnosis comes too late for a patient to be eligible for surgery due to the tendency of the tumors to become intertwined with major organs and blood vessels.” 

“Once this goes to clinical trials, it could shift the paradigm for pancreatic cancer treatments – or any other solid tumors where standard IV chemotherapy drugs are hard to get to,” said Jen Jen Yeh, associate professor of surgery and pharmacology in UNC’s School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. 

James Byrne, a member of DeSimone’s lab at UNC-Chapel Hill, led the research by constructing the device and examining its ability to deliver chemotherapeutic drugs effectively to pancreatic cancer tumors, as well as two types of breast cancer tumors. 

Depending on the tumor type, the new device can be used either internally after a minimally invasive surgery to implant the device’s electrodes directly on a tumor (an approach relevant especially for pancreatic cancer and other less accessible tumors) or externally to deliver drugs through the skin (an approach relevant especially for treating inflammatory breast cancers and other accessible tumors such as head and neck cancers). 

Researchers have also demonstrated the device’s ability to enable higher drug concentrations in tumor tissue while avoiding increased systemic toxicity. This is especially important in treating pancreatic and other solid tumors, which are not well vascularized and are thus difficult to reach using standard treatment methods that rely on the bloodstream for delivering cancer-fighting drugs to tumors. 

“Progress in the treatment of pancreatic cancer has been persistent but incremental in the past few decades, relying largely on advances in drug therapies. To our knowledge, our study represents the first time iontophoresis has been applied to target pancreatic cancer,” said Byrne, who is currently completing his medical degree at UNC-Chapel Hill after earning his doctorate in 2014 as a member of the DeSimone lab. 

“We hope our invention can be used in humans in the coming years and result in a notable increase in life expectancy and quality among patients diagnosed with pancreatic and other types of cancer,” added Byrne. 

The work was funded in part by the University Cancer Research Fund and the National Institutes of Health’s Director’s Pioneer Award Program. Collaboration among researchers at the UNC Eshelman School of Pharmacy, UNC School of Medicine, Lineberger Comprehensive Cancer Center and the UNC College of Arts and Sciences made the work possible. 

Media note: Joseph M. DeSimone can be reached at .

Communications and Public Affairs contact: Thania Benios, (919) 962 – 8596, thania_benios@unc.edu 


Potential pancreatic cancer treatment could increase life expectancy
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Compared to a control (left), mice treated with a chemotherapy drug using the device experienced significant growth reduction as confirmed by the lack of brown staining for a marker of tumor growth.

Potential pancreatic cancer treatment could increase life expectancy
Current image JPEG image — 323 KB

Joseph DeSimone, PhD (L) and James Byrne, PhD (R)/Photo: UNC Eshelman School of Pharmacy

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Potential pancreatic cancer treatment could increase life expectancy

Device that drives drugs into solid tumors that are poorly vascularized opens the possibility of life-saving surgeries in cancer patients.
Potential pancreatic cancer treatment could increase life expectancy click to enlarge Compared to a control (left), mice treated with a chemotherapy drug using the device experienced significant growth reduction as confirmed by the lack of brown staining for a marker of tumor growth.
Potential pancreatic cancer treatment could increase life expectancy click to enlarge Joseph DeSimone, PhD (L) and James Byrne, PhD (R)/Photo: UNC Eshelman School of Pharmacy

Pancreatic cancer cells are notorious for being protected by a fortress of tissue, making it difficult to deliver drugs to either shrink the tumor or stop its growth. Now researchers at the University of North Carolina at Chapel Hill have developed a device that could change all that: By using electric fields, the device can drive chemotherapy drugs directly into tumors, preventing their growth and in some cases, shrinking them. 

The work, published Feb. 4 in Science Translational Medicine, opens the possibility of dramatically increasing the number of people who are eligible for life-saving surgeries. It represents a fundamentally new treatment approach for pancreatic cancer, which has a 75 percent mortality rate within a year of diagnosis - a statistic that has not changed in more than 40 years. 

“Surgery to remove a tumor currently provides the best chance to cure pancreatic cancer,” said Joseph DeSimone, who is Chancellor’s Eminent Professor of Chemistry at UNC and William R. Kenan, Jr. Distinguished Professor of Chemical Engineering at NC State University. “However, often a diagnosis comes too late for a patient to be eligible for surgery due to the tendency of the tumors to become intertwined with major organs and blood vessels.” 

“Once this goes to clinical trials, it could shift the paradigm for pancreatic cancer treatments – or any other solid tumors where standard IV chemotherapy drugs are hard to get to,” said Jen Jen Yeh, associate professor of surgery and pharmacology in UNC’s School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. 

James Byrne, a member of DeSimone’s lab at UNC-Chapel Hill, led the research by constructing the device and examining its ability to deliver chemotherapeutic drugs effectively to pancreatic cancer tumors, as well as two types of breast cancer tumors. 

Depending on the tumor type, the new device can be used either internally after a minimally invasive surgery to implant the device’s electrodes directly on a tumor (an approach relevant especially for pancreatic cancer and other less accessible tumors) or externally to deliver drugs through the skin (an approach relevant especially for treating inflammatory breast cancers and other accessible tumors such as head and neck cancers). 

Researchers have also demonstrated the device’s ability to enable higher drug concentrations in tumor tissue while avoiding increased systemic toxicity. This is especially important in treating pancreatic and other solid tumors, which are not well vascularized and are thus difficult to reach using standard treatment methods that rely on the bloodstream for delivering cancer-fighting drugs to tumors. 

“Progress in the treatment of pancreatic cancer has been persistent but incremental in the past few decades, relying largely on advances in drug therapies. To our knowledge, our study represents the first time iontophoresis has been applied to target pancreatic cancer,” said Byrne, who is currently completing his medical degree at UNC-Chapel Hill after earning his doctorate in 2014 as a member of the DeSimone lab. 

“We hope our invention can be used in humans in the coming years and result in a notable increase in life expectancy and quality among patients diagnosed with pancreatic and other types of cancer,” added Byrne. 

The work was funded in part by the University Cancer Research Fund and the National Institutes of Health’s Director’s Pioneer Award Program. Collaboration among researchers at the UNC Eshelman School of Pharmacy, UNC School of Medicine, Lineberger Comprehensive Cancer Center and the UNC College of Arts and Sciences made the work possible. 

Media note: Joseph M. DeSimone can be reached at .

Communications and Public Affairs contact: Thania Benios, (919) 962 – 8596, thania_benios@unc.edu 

UNC Lineberger analysis finds that advanced age should not limit cancer treatment

After comparing the survival outcomes of older and younger people with head and neck cancer, UNC Lineberger researchers have found that age alone shouldn’t dictate a patient’s treatment. The findings were published January 12 online in the journal The Oncologist.

“What we should take away from this is that age alone shouldn’t impact the treatment of patients with head and neck cancer,” said José P. Zevallos, MD, MPH, FACS, an assistant professor at the UNC School of Medicine and a paper author.

For the study, the researchers analyzed data from the UNC Cancer Registry database for 1,447 patients who had been diagnosed with head and neck cancer between 1990 and 2005. In one analysis, they looked at survival outcomes for a subset of patients with a particular type of head and neck cancer -- larynx cancer – and grouped by age, cancer stage and level of treatment. 

A key finding from that analysis was that older patients at or above the age of 70 years with both early and late-stage cancers had similar cancer-specific outcomes compared to their younger counterparts when receiving stage-appropriate treatment.

In advanced cancers, this often meant multimodality treatment – which involves using a combination of surgery, radiation therapy, and/or chemotherapy. The study found that advanced-stage cancer patients who received multimodality treatment had survival outcomes that were “essentially identical” to those of younger patients.

In patients with early-stage cancer, the researchers found that older patients had worse overall survival and worse progression-free survival outcomes compared with the younger group. But because there was no significant difference in the rates that cancer returned in older and younger patients, the researchers believe that competing health factors involved in that finding.

“When you actually look at the data in more detail, you find that there are competing causes of mortality -- which means that the older patients are dying of reasons other than their head and neck cancer,” Zevallos said.

In patients with advanced cancers, patients at or above age 70 with later-stage cancer who received only one therapy – either surgery or radiation alone – had very poor outcomes compared with all other patients.

“This finding highlights the importance of multi-modality treatment irrespective of patient age,” Zevallos said. “However, it also demonstrates that patient co-morbidities and treatment tolerability impact survival among older patients with advanced head and neck cancer.”

“This study is another of the many examples showing that age alone should not be used to select treatment for older cancer patients,” said Hyman Muss, MD, a professor of medicine, director of UNC Lineberger’s Geriatric Oncology Program and a study author. “Reasonably healthy older patients should be offered the same state-of-the-art treatment options as the younger colleagues.”

Zevallos said he believes the study topic will be an area of increasing relevance and importance as the population ages. According to National Cancer Institute Surveillance, Epidemiology, and End Results Program data from 2007-2011, the median age of diagnosis for all cancers is 66. The paper said there have been few studies focused on the characteristics and treatment of older patients with squamous cell carcinomas of the head and neck.

Read the paper.

UNC Board of Trustees chair and cancer survivor Lowry Caudill headlines 28th Annual Lineberger Club event

Nearly 300 UNC Lineberger Comprehensive Cancer Center supporters gathered at the Carolina Inn to hear the remarks of distinguished UNC alumnus Lowry Caudill, PhD, on January 24, 2015 during the 28th Annual Lineberger Club Lunch and Basketball Game.

Caudill, chair of the UNC Board of Trustees and of the University’s Innovation Circle was also co-president and co-founder of Magellan Laboratories, Incorporated, a Research Triangle Park based pharmaceutical development company. He received a B.S. in chemistry from the University of North Carolina at Chapel Hill in 1979 and went on to earn a PhD in analytical chemistry from Indiana University in 1983. A true blue Tar Heel, Caudill has served the University he loves throughout his life as a leader, teacher, parent and ardent supporter.

When Caudill was diagnosed with prostate cancer in 2009, he had the ability to go anywhere in the country for his care. He felt he had a duty to his wife Suzi and their three children to seek out the best treatment available. Using his years of experience as a scientist, he thoroughly researched his options and concluded that the best treatment in the country was available at UNC Lineberger with urologic oncologist Eric Wallen, MD.

Prostate cancer is a complex disease with a variety of treatment options. Wallen took the time to carefully explain and discuss the options with Caudill, and together they decided on the best course of treatment. In February 2010, Wallen performed a robotic assisted laparoscopic prostatectomy. Caudill had no complications from the surgery and has been cancer free for five years.

Caudill credits his successful outcome to skilled and compassionate physicians and UNC Lineberger’s team approach to cancer care.  Speaking of Wallen, Caudill said with emotion, “not only did he give me quality of life, he saved my life.”

Caudill also spoke movingly of the care received by his mother, Jacqueline Lowry Caudill, at UNC Lineberger when she was diagnosed with a soft tissue sarcoma in 2011 at the age of 85. Speaking of her care team, which included radiation oncologist Joel Tepper, MD, and medical oncologist Juneko Grilley-Olson, MD, Caudill said the amazing care they provided gave his mother three years with a high quality of life before she passed away in December 2014 at the age of 88.

“You gave my mom to us for three more years,” he said. “Three years we didn’t think we would have, and what a gift that was.” 

As chair of the Board of Trustees, Caudill has what he calls “the best seat in the house” to see all the great things that are happening at Carolina. He spoke with pride of the strides in translational research and its impact on the people of North Carolina noting that UNC Lineberger is leading that front. “As board chair and as an alum,” he said, “I am very proud of what we are doing here. As someone who has benefited personally from it, I am forever grateful.”   

Each year, UNC Lineberger hosts the Lineberger Club Lunch and Basketball Game, inviting its most loyal and generous supporters.  UNC Lineberger is grateful to Lee-Moore Capital Company, Dual Comfort Heating and Air Conditioning and Hardee’s for making the 28th annual event possible.

UNC Board of Trustees chair and cancer survivor Lowry Caudill headlines 28th Annual Lineberger Club event

Nearly 300 UNC Lineberger Comprehensive Cancer Center supporters gathered at the Carolina Inn to hear the remarks of distinguished UNC alumnus Lowry Caudill, PhD, on January 24, 2015 during the 28th Annual Lineberger Club Lunch and Basketball Game.

Caudill, chair of the UNC Board of Trustees and of the University’s Innovation Circle was also co-president and co-founder of Magellan Laboratories, Incorporated, a Research Triangle Park based pharmaceutical development company. He received a B.S. in chemistry from the University of North Carolina at Chapel Hill in 1979 and went on to earn a PhD in analytical chemistry from Indiana University in 1983. A true blue Tar Heel, Caudill has served the University he loves throughout his life as a leader, teacher, parent and ardent supporter.

When Caudill was diagnosed with prostate cancer in 2009, he had the ability to go anywhere in the country for his care. He felt he had a duty to his wife Suzi and their three children to seek out the best treatment available. Using his years of experience as a scientist, he thoroughly researched his options and concluded that the best treatment in the country was available at UNC Lineberger with urologic oncologist Eric Wallen, MD.

Prostate cancer is a complex disease with a variety of treatment options. Wallen took the time to carefully explain and discuss the options with Caudill, and together they decided on the best course of treatment. In February 2010, Wallen performed a robotic assisted laparoscopic prostatectomy. Caudill had no complications from the surgery and has been cancer free for five years.

Caudill credits his successful outcome to skilled and compassionate physicians and UNC Lineberger’s team approach to cancer care.  Speaking of Wallen, Caudill said with emotion, “not only did he give me quality of life, he saved my life.”

Caudill also spoke movingly of the care received by his mother, Jacqueline Lowry Caudill, at UNC Lineberger when she was diagnosed with a soft tissue sarcoma in 2011 at the age of 85. Speaking of her care team, which included radiation oncologist Joel Tepper, MD, and medical oncologist Juneko Grilley-Olson, MD, Caudill said the amazing care they provided gave his mother three years with a high quality of life before she passed away in December 2014 at the age of 88.

“You gave my mom to us for three more years,” he said. “Three years we didn’t think we would have, and what a gift that was.” 

As chair of the Board of Trustees, Caudill has what he calls “the best seat in the house” to see all the great things that are happening at Carolina. He spoke with pride of the strides in translational research and its impact on the people of North Carolina noting that UNC Lineberger is leading that front. “As board chair and as an alum,” he said, “I am very proud of what we are doing here. As someone who has benefited personally from it, I am forever grateful.”   

Each year, UNC Lineberger hosts the Lineberger Club Lunch and Basketball Game, inviting its most loyal and generous supporters.  UNC Lineberger is grateful to Lee-Moore Capital Company, Dual Comfort Heating and Air Conditioning and Hardee’s for making the 28th annual event possible.






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Basch calls for more data on prostate cancer detection technology in JAMA editorial

A UNC Lineberger researcher has pointed to a need for more data on whether new technology designed to better detect men at higher-risk for prostate cancer will also mean improvements in survival rates and symptoms.
Basch calls for more data on prostate cancer detection technology in JAMA editorial click to enlarge Ethan Basch, MD

Ethan Basch, MD, an associate professor at the University of North Carolina at Chapel Hill School of Medicine and a UNC Lineberger Comprehensive Cancer Center member, was one of two authors on the editorial, which was published online Tuesday in The Journal of the American Medical Association. Basch is also an associate editor for the journal.

The editorial was a reaction to a study also published Tuesday in JAMA that showed that a new biopsy technique that combines magnetic resonance imaging (MRI) with ultrasound was more effective in detecting high-risk prostate cancer.

According to a news release, the study found that 30 percent more high-risk prostate cancers were diagnosed with the new technique -- called targeted fusion-guided biopsy -- than with standard biopsy. In addition, 17 percent fewer low-risk cancers were diagnosed with the new approach, compared to the older method. More than 1,000 men participated in the research at the National Institutes of Health (NIH) over a seven-year period.

Prostate cancer screening has come under scrutiny, with researchers asking whether benefits of early screening and intervention based on those findings outweigh potential harms -- as some treatments can impact men’s sexual, bowel or urinary function. The biopsy is the second step in the prostate cancer diagnostic process after an initial blood-test called the prostate-specific antigen, or PSA test. The U.S. Preventive Services Task Force recommended against PSA screening for men of all ages 2012, and other groups have revised their screening recommendations.

In the editorial, Basch and his co-author Lawrence H. Schwartz, MD, a professor of radiology with the Columbia University College of Physicians and Surgeons, said the results of the study on the new targeted fusion biopsy technique are “compelling” and that improvement in of the accuracy of high-grade tumor detection is needed.

“This is a new approach that helps us better classify cancers as higher risk or lower risk,” Basch said. “Intuitively, it seems like a helpful test for decision making.”

But the editorial also says it isn’t yet known whether the new biopsy technique will also translate into meaningful outcomes for patients, such as benefits in symptoms, functional status or survival.

“Without conducting a randomized study or a well-conducted, large, observational study demonstrating the benefits of a new test, I feel we’re still a step away from understanding if it’s really worth it,” he said.

 Read the editorial here 

Her First Thought

When a young woman receives a cancer diagnosis, her obvious first thought is “I want to survive this.” When that cancer diagnosis has an impact on her ability to have children, she has a second thought.

Tonya Caldwell was just 25 years old when she received a diagnosis of stage IB cervical cancer. Most women with that diagnosis are treated with hysterectomy. “I was devastated,” she recalls. “I didn’t know what to do, what to think – and I was told I may never have children.” As hard as it was to hear she had cancer, it was even harder to for her to hear she might never have children.

Crystal Lasonde hadn’t thought much about motherhood prior to her diagnosis of cervical cancer in 2011. Only 31 at the time, she was focused on her marriage and career. So frightening was the diagnosis of cancer, that the possibility of losing the ability to have children didn’t cross her mind. “I was scared because I had cancer, so I didn’t think about it,” she says.

Fortunately, Caldwell and Lasonde were referred to Dr. John Boggess, at UNC Lineberger Comprehensive Cancer Center. Boggess is one of a small number of doctors in the U.S. offering another procedure to young cervical cancer patients known as a trachelectomy. This surgery removes the cervix, nearby lymph nodes and the upper part of the vagina. The uterus and ovaries remain intact thus preserving fertility. Following a trachelectomy, women are often able to carry a pregnancy to term and deliver by cesarean section.

Caldwell was thrilled to have a treatment option that could preserve her ability to bear children. She was told that the surgical team would go in with the intention to remove only the cervix and surrounding lymph nodes. However, she was cautioned that if they saw the cancer had spread, they would have to perform a hysterectomy.

She recalls that the first words she spoke when she woke from surgery were “Can I have kids?” And happily, the answer was “Yes!”

Six years after her diagnosis of cervical cancer, Caldwell and her husband are parents of one year old Eli.

Caldwell’s obstetrician had never taken care of a patient without a cervix before and wasn’t quite sure what to expect. Some extra precautions were taken including progesterone injections and frequent ultrasound examinations. Caldwell says that Dr. Boggess’ surgical work was so good that one ultrasound technician couldn’t believe that she didn’t have a cervix because it looked like she had a complete cervix on the ultrasound.

Lasonde was also happy to have a fertility-sparing treatment option, but she says she didn’t fully appreciate it until she and her husband welcomed their son, Jacob in 2014. “I think it’s so cool that I was able to become a mother!” she says. “I love it! I didn’t think I would love it this much. People tell you that you’re never going to experience love like this, but you don’t really understand. Then it happens, and it’s just the coolest thing ever.”

Boggess was among the first to hear the news of Caldwell and Lasonde’s pregnancies. Both women say that he was as excited as they were.

Boggess still watches the new moms closely. He followed their progress throughout their pregnancies and has met both Jacob and Eli. “Every time I see him he gives me a high five and a big hug. He’s a very good man,” Caldwell says with emotion.

Caldwell wants others to know that there is hope for young cervical cancer patients saying, “It’s not the end of the world. It is devastating to hear, but there is something that can be done.”

“Eli is truly our miracle baby,” says Caldwell. “I am overjoyed,” she says. “I always wanted to be a mom, and I’m a mom now.” And soon, Eli will be a big brother. Caldwell is expecting her second child later this year.

The American Cancer Society estimates that more than 12,000 new cases of invasive cervical cancer will be diagnosed in the United States this year. Although cervical cancer is rare in young women, the common surgical treatment (hysterectomy) leaves them unable to bear children.

Her First Thought

When a young woman receives a cancer diagnosis, her obvious first thought is “I want to survive this.” When that cancer diagnosis has an impact on her ability to have children, she has a second thought.

Tonya Caldwell was just 25 years old when she received a diagnosis of stage IB cervical cancer. Most women with that diagnosis are treated with hysterectomy. “I was devastated,” she recalls. “I didn’t know what to do, what to think – and I was told I may never have children.” As hard as it was to hear she had cancer, it was even harder to for her to hear she might never have children.

Crystal Lasonde hadn’t thought much about motherhood prior to her diagnosis of cervical cancer in 2011. Only 31 at the time, she was focused on her marriage and career. So frightening was the diagnosis of cancer, that the possibility of losing the ability to have children didn’t cross her mind. “I was scared because I had cancer, so I didn’t think about it,” she says.

Fortunately, Caldwell and Lasonde were referred to Dr. John Boggess, at UNC Lineberger Comprehensive Cancer Center. Boggess is one of a small number of doctors in the U.S. offering another procedure to young cervical cancer patients known as a trachelectomy. This surgery removes the cervix, nearby lymph nodes and the upper part of the vagina. The uterus and ovaries remain intact thus preserving fertility. Following a trachelectomy, women are often able to carry a pregnancy to term and deliver by cesarean section.

Caldwell was thrilled to have a treatment option that could preserve her ability to bear children. She was told that the surgical team would go in with the intention to remove only the cervix and surrounding lymph nodes. However, she was cautioned that if they saw the cancer had spread, they would have to perform a hysterectomy.

She recalls that the first words she spoke when she woke from surgery were “Can I have kids?” And happily, the answer was “Yes!”

Six years after her diagnosis of cervical cancer, Caldwell and her husband are parents of one year old Eli.

Caldwell’s obstetrician had never taken care of a patient without a cervix before and wasn’t quite sure what to expect. Some extra precautions were taken including progesterone injections and frequent ultrasound examinations. Caldwell says that Dr. Boggess’ surgical work was so good that one ultrasound technician couldn’t believe that she didn’t have a cervix because it looked like she had a complete cervix on the ultrasound.

Lasonde was also happy to have a fertility-sparing treatment option, but she says she didn’t fully appreciate it until she and her husband welcomed their son, Jacob in 2014. “I think it’s so cool that I was able to become a mother!” she says. “I love it! I didn’t think I would love it this much. People tell you that you’re never going to experience love like this, but you don’t really understand. Then it happens, and it’s just the coolest thing ever.”

Boggess was among the first to hear the news of Caldwell and Lasonde’s pregnancies. Both women say that he was as excited as they were.

Boggess still watches the new moms closely. He followed their progress throughout their pregnancies and has met both Jacob and Eli. “Every time I see him he gives me a high five and a big hug. He’s a very good man,” Caldwell says with emotion.

Caldwell wants others to know that there is hope for young cervical cancer patients saying, “It’s not the end of the world. It is devastating to hear, but there is something that can be done.”

“Eli is truly our miracle baby,” says Caldwell. “I am overjoyed,” she says. “I always wanted to be a mom, and I’m a mom now.” And soon, Eli will be a big brother. Caldwell is expecting her second child later this year.

The American Cancer Society estimates that more than 12,000 new cases of invasive cervical cancer will be diagnosed in the United States this year. Although cervical cancer is rare in young women, the common surgical treatment (hysterectomy) leaves them unable to bear children.






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UNC researcher co-leads effort to map genomic changes in head and neck cancer

A study co-led by a UNC Lineberger Comprehensive Cancer Center researcher has identified genomic changes in head and neck cancers linked to the sexually transmitted disease HPV -- the latest finding of a collaborative scientific effort designed to map out the genomic changes driving cancer.
UNC researcher co-leads effort to map genomic changes in head and neck cancer click to enlarge TCGA researchers have uncovered new details about the potential role of the human papillomavirus (HPV) in head and neck cancer. HPV-related head and neck cancers have been growing in number. Credit: Ernesto del Aguila, NHGRI.

The study by The Cancer Genome Atlas (TCGA) researchers analyzed the genomes of 279 head and neck cancer tumors. They identified subtypes of head and neck cancer based on their genomic characteristics, changes in smoking-related tumors, as well as genomic differences in head and neck cancer tumors linked to HPV, the most commonly sexually transmitted disease in the United States.

The findings were published online Wednesday in the journal Nature. Researchers hope the findings will help lead to potential new therapies and the identification of markers that can help identify patients likely to respond to a particular therapy, as well as help direct the best course of treatment for patients.

“The rapid increase in HPV-related head and neck cancers, noticeably in oropharyngeal tumors, has created an even greater sense of urgency in the field,” said D. Neil Hayes, MD, MPH, senior author of the study report, an associate professor of medicine at the University of North Carolina School of Medicine and a member of UNC Lineberger. Oropharyngeal cancer starts in the oropharynx, which is the part of the throat behind the mouth. “We’re uncovering differences between tumors with and without HPV infection, and these new data are allowing us to rethink how we approach head and neck cancers.”

Smoking and alcohol use are main risk factors for head and neck cancer, according to the National Cancer Institute (NCI). But studies have shown that HPV-linked oropharyngeal cancer cases are on the rise. About 9,000 new oropharyngeal cancer cases are estimated to have been caused by HPV in the United States each year, according to the Centers for Disease Control and Prevention.

Comparatively, there were an estimated 55,000 new cases last year of all types of head and neck cancer, which include tumors of the mouth, throat, voice box, nasal cavity and salivary gland.1 In North Carolina, there were 1,850 new cases of head and neck cancer in 2012, which was up about 3 percent from 2011.2

In the HPV positive tumors in their sample, they found tumors with deletions and mutations of a gene called TRAF3, which is involved in anti-viral response. The researchers also found alterations of the FGFR3 gene and mutations in the PIK3CA gene in HPV positive tumors, which are also found in a much broader set of mutations in smoking-related tumors. PIK3CA has already been shown to be associated with HPV, Hayes said, but he said they showed the link clearly in their study.

And the study found that while the EGFR (epidermal growth factor receptor) gene is frequently altered in HPV-negative tumors in smokers, it is rarely abnormal in HPV-positive tumors.

They found that many of the head and neck cancer tumors in the study had alterations in a group of genes for certain growth factor receptors such as EGFR and FGFR, signaling molecules, and cell division regulation.

“So this is a set of alterations that, at some level, many people think are drug-able,” Hayes said. He called attention to the study’s findings for one gene in particular, CCND1, that’s involved in cell division regulation. Hayes said the gene is involved in a drug-able pathway, and a potential drug is in development for it.

In addition to helping understand genomic changes in head and neck cancer, Hayes also said the study’s findings may also help further the understanding of other cancer types.

And while Hayes said TCGA efforts have helped create a “parts list” of genomic alternations in a range of cancers, he said there are cancer types for which more genomic mapping is needed.

 “Just like in a car manual, you need to know what kind of car you have and what the parts are to know how to put it back together,” Hayes said. “We really have built a parts manual for what’s broken in cancer so that we can start addressing it in a logical and a real way.”

The Cancer Genome Atlas is supported and managed by the NCI and the National Human Genome Research Institute. The TCGA network includes researchers at institutions around the country and globe.

As national leaders in TCGA, UNC Lineberger scientists have been involved in multiple, individual tissue type studies as well as the largest, most diverse tumor genetic analysis ever conducted to date. UNC has done RNA sequencing work for those projects, among other contributions.

The study was funded by grants from the National Institutes of Health, the Bobby F. Garrett Cancer Foundation and NIDCD Intramural Projects.

Reference: The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of head and neck squamous cell carcinomasNature. Online January 28, 2015. DOI: 10.1038/nature14129.

About The Cancer Genome Atlas (TCGA) Research Network

TCGA is jointly funded and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health.  TCGA-generated data are freely available in advance of publication at the TCGA Data Portal, http://tcga-data.nci.nih.gov/tcga, and CGHub, https://cghub.ucsc.edu.

The TCGA Research Network includes more than 150 researchers at dozens of institutions across the nation. A list of participants is available at cancergenome.nih.gov/abouttcga/overview. More details about TCGA, including Quick Facts, Q&A, graphics, glossary, a brief guide to genomics and a media library of images can be found at cancergenome.nih.gov.

About UNC Lineberger

One of only 41 NCI-designated comprehensive cancer centers, the University of North Carolina Lineberger Comprehensive Cancer Center brings together some of the most exceptional physicians and scientists in the country to investigate and improve the prevention, early detection and treatment of cancer. With research that spans the spectrum from the laboratory to the bedside to the community, UNC Lineberger faculty work to understand the causes of cancer at the genetic and environmental levels, to conduct groundbreaking laboratory research, and to translate findings into pioneering and innovative clinical trials. For more information, please visit www.unclineberger.org.   

1. National Cancer Institute Surveillance, Epidemiology, and End Results Program, 2015.
2. North Carolina Cancer Registry, 2015.

Media Contact: Laura Oleniacz, UNC Lineberger Comprehensive Cancer Center, at loleniac@email.unc.edu  919-812-0621

Researchers pinpoint two genes that trigger severest form of ovarian cancer

UNC geneticists create the first mouse model of ovarian clear cell carcinoma; show how a known drug can suppress tumor growth.

In the battle against ovarian cancer, UNC School of Medicine researchers have created the first mouse model of the worst form of the disease and found a potential route to better treatments and much-needed diagnostic screens.

Led by Terry Magnuson, PhD, the Sarah Graham Kenan Professor and chair of the department of genetics, a team of UNC genetics researchers discovered how two genes interact to trigger cancer and then spur on its development.

“It’s an extremely aggressive model of the disease, which is how this form of ovarian cancer presents in women,” said Magnuson, who is also a member of the UNC Lineberger Comprehensive Cancer Center. Not all mouse models of human diseases provide accurate depictions of the human condition. Magnuson’s mouse model, though, is based on genetic mutations found in human cancer samples.

Mutations in two genes –ARID1A and PIK3CA – were previously unknown to cause cancer. “When ARID1A is less active than normal and PIK3CA is overactive,” Magnuson said, “the result is ovarian clear cell carcinoma 100 percent of the time in our model.”

The research also showed that a drug called BKM120, which suppresses PI3 kinases, directly inhibited tumor growth and significantly prolonged the lives of mice. The drug is currently being tested in human clinical trials for other forms of cancer.

The work, published today in the journal Nature Communications, was spearheaded by Ron Chandler, PhD, a postdoctoral fellow in Magnuson’s lab. Chandler had been studying the ARID1A gene – which normally functions as a tumor suppressor in people – when results from cancer genome sequencing projects showed that the ARID1A gene was highly mutated in several types of tumors, including ovarian clear cell carcinoma. Chandler began researching the gene’s precise function in that disease and found that deleting it in mice did not cause tumor formation or tumor growth.

Read the full story. 


Researchers pinpoint two genes that trigger severest form of ovarian cancer
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Terry Magnuson, PhD/ Photo by Max Englund, UNC Health Care)

Researchers pinpoint two genes that trigger severest form of ovarian cancer
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Ron Chandler, PhD

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Researchers pinpoint two genes that trigger severest form of ovarian cancer

UNC geneticists create the first mouse model of ovarian clear cell carcinoma; show how a known drug can suppress tumor growth.
Researchers pinpoint two genes that trigger severest form of ovarian cancer click to enlarge Terry Magnuson, PhD/ Photo by Max Englund, UNC Health Care)
Researchers pinpoint two genes that trigger severest form of ovarian cancer click to enlarge Ron Chandler, PhD

In the battle against ovarian cancer, UNC School of Medicine researchers have created the first mouse model of the worst form of the disease and found a potential route to better treatments and much-needed diagnostic screens.

Led by Terry Magnuson, PhD, the Sarah Graham Kenan Professor and chair of the department of genetics, a team of UNC genetics researchers discovered how two genes interact to trigger cancer and then spur on its development.

“It’s an extremely aggressive model of the disease, which is how this form of ovarian cancer presents in women,” said Magnuson, who is also a member of the UNC Lineberger Comprehensive Cancer Center. Not all mouse models of human diseases provide accurate depictions of the human condition. Magnuson’s mouse model, though, is based on genetic mutations found in human cancer samples.

Mutations in two genes –ARID1A and PIK3CA – were previously unknown to cause cancer. “When ARID1A is less active than normal and PIK3CA is overactive,” Magnuson said, “the result is ovarian clear cell carcinoma 100 percent of the time in our model.”

The research also showed that a drug called BKM120, which suppresses PI3 kinases, directly inhibited tumor growth and significantly prolonged the lives of mice. The drug is currently being tested in human clinical trials for other forms of cancer.

The work, published today in the journal Nature Communications, was spearheaded by Ron Chandler, PhD, a postdoctoral fellow in Magnuson’s lab. Chandler had been studying the ARID1A gene – which normally functions as a tumor suppressor in people – when results from cancer genome sequencing projects showed that the ARID1A gene was highly mutated in several types of tumors, including ovarian clear cell carcinoma. Chandler began researching the gene’s precise function in that disease and found that deleting it in mice did not cause tumor formation or tumor growth.

Read the full story. 

Hoadley and Perou research featured in ASCO annual review

Research led by UNC Lineberger Comprehensive Cancer Center members Katherine Hoadley, PhD, research assistant professor in genetics and Chuck Perou, PhD, professor of genetics and pathology, was selected by the American Society of Clinical Oncology for inclusion in Clinical Cancer Advances 2015, the Society’s annual review of progress against cancer and emerging trends in the field. The study, a comprehensive tumor genetic analysis which revealed a new way of classifying cancers, is featured as one of the year’s major achievements in clinical cancer research and care.
Hoadley and Perou research featured in ASCO annual review click to enlarge Katherine Hoadley, PhD and Chuck Perou, PhD

Hoadley, Perou and other researchers with The Cancer Genome Atlas (TCGA) Research Network analyzed more than 3,500 tumors across 12 different tissue types and 6 different data platforms to see how they compared to one another -- the largest data set of tumor genomics ever assembled, explained lead author Hoadley. They found that cancers are more likely to be genetically similar based on the type of cell in which the cancer originated and not necessarily the type of tissue in which it originated.

“In some cases, a single cell type makes up the tissue from which the tumor originates,” said Hoadley. “But in other cases, the tissue in which the cancer originates is made up of multiple types of cells that can each give rise to tumors. Understanding the cell in which the cancer originates appears to be very important in determining the subtype of a tumor and, in turn, how that tumor behaves and how it should be treated.”

The study not only revamps traditional ideas of how cancers are diagnosed and treated, but could also have a profound impact on the future landscape of drug development. Hoadley and Perou explain that the development of drugs may now focus on targeting larger groups of cancers with genomic similarities, as opposed to a single tumor type as they are currently developed.

Developed under the guidance of an expert editorial board, Clinical Cancer Advances (CCA) is an independent annual review of the year’s major achievements and emerging trends in clinical cancer research and care. To learn more, read the report at www.cancerprogress.net/CCA.

Gershon, Gama named 2015 recipients of Weatherspoon Family Brain Tumor Research Award

Timothy R. Gershon, MD, PhD, and Vivian Gama, PhD, have been announced as the 2015 recipients of the Weatherspoon Family Brain Tumor Research Award.
Gershon, Gama named 2015 recipients of Weatherspoon Family Brain Tumor Research Award click to enlarge Timothy R. Gershon, MD, PhD, and Vivian Gama, PhD

Dr. Gershon, an assistant professor in the UNC School of Medicine Department of Neurology and a UNC Lineberger member, is being recognized for his research exploring why radiation therapy works for some people with medulloblastoma, the most common malignant tumor type in children, and not in others.

Using a technique for giving radiation therapy to genetically-altered mice, he and his colleagues were able to show that medulloblastomas respond to radiation if their “self-destruct” system is intact. Unlike other cancers, medulloblastomas usually lack mutations that completely block the mechanisms of cell death. This work was published in a 2013 paper in the Journal of Neuroscience and a second manuscript is currently in review. Work is ongoing in his lab to determine how mutations that make medulloblastomas radiation-resistant can be targeted.

Dr. Gama, a postdoctoral fellow with the UNC Neuroscience Center in the lab of Mohanish Deshmukh, PhD, a professor in the UNC School of Medicine Department of Cell Biology and Physiology, was part of a group that made the discovery of a new mechanism for how neurons and brain cancer cells avoid self-destruction. They identified a protein called PARC as the agent responsible for degrading cytochrome c, a key trigger of cell death. She led the experiments in cell cultures and in animals for the study, which was published in Science Signaling last year. Their work also identified PARC as a new therapeutic target.

“These researchers are involved in groundbreaking research that has the potential to lead to improved brain tumor treatments and new treatment targets,” said Matthew Ewend, MD, chair of the Department of Neurosurgery, which gives the research award. “They are truly deserving of this recognition for their efforts, which could improve the lives of many.”

The Weatherspoon Family Brain Tumor Research Award was created in 2011 to honor Van Weatherspoon of Charlotte. It recognizes his ongoing commitment and years of service to UNC-Chapel Hill and its brain tumor program.

UNC Health Registry Partnership results in new research publications

In partnership with clinical investigators in gynecologic oncology, the UNC Health Registry/Cancer Survivorship Cohort (HR/CSC) provided recruitment, data collection through patient interviews, and support for multiple publications.

The UNC Health Registry/Cancer Survivorship Cohort (HR/CSC) provided recruitment, data collection through patient interviews, and support for the following publications: 

Doll KM, Kalinowski AK, Snavely AC, Irwin DE, Bensen JT, Bae-Jump VL, Kim KH, Van Le L, Clarke-Pearson DL, Gehrig PA. Obesity is associated with worse quality of life in women with gynecologic malignancies: An opportunity to improve patient-centered outcomes. Cancer. 2014 Sep 23. doi: 10.1002/cncr.29061. [Epub ahead of print] 

Doll, KM, Snavely, AC, Klinowski A, Irwin DE, Bensen JT, Bae-Jump V, Soper JT, Brewster WR, Gehrig PA. Preoperative quality of life and surgical outcomes in gynecologic oncology patients: A new predictor of operative risk? Gynecol Oncol. 2014 Jun;133(3):546-51. doi: 10.1016/j.ygyno.2014.04.002  

Visit the UNC Health Registry/Cancer Survivorship Cohort (HR/CSC) website to see what resources and services we have to support your research.