Beyond The
bench Two Thousand Sixteen
The University of Kansas
Cancer Center
Randall O’Donnell, Ph.D., President and Chief Executive Officer of Children’s Mercy, Roy Jensen, M.D., Director of The University of Kansas Cancer Center, David Chao, Ph.D., President and Chief Executive Officer of Stowers Institute for Medical Research
Director’s overview and other resources. Last year, KU Cancer Center and Children’s Mercy combined its pediatric oncology departments. With this partnership, all ages, from children to the elderly, are covered. It’s an exciting time for KU Cancer Center and our community. We recently submitted our request for National Cancer Institute designation renewal, which is required every five years. In our application, we asked to be considered for Comprehensive designation, the most elite designation available to a cancer center. Comprehensive centers demonstrate an added depth and breadth of research, as well as substantial transdisciplinary research that bridges all scientific areas. It also requires a greater emphasis on preventing cancer through education, prevention and early detection. We have been working towards Comprehensive status for years, and it’s now within our reach.
Early on, we recognized that in order to move closer towards a world without cancer, we first had to step back for a broader view, beyond the walls of our laboratories. From deepening our understanding of cancer’s biology to expanding cancer prevention efforts to ensuring patients’ care continues after treatment, we are tackling cancer on multiple fronts. In these pages, we report on the progress we have made at the forefront of cancer research, including the development of new therapies. I’m excited for you to learn about a potential “first” for KU Cancer Center – a cancer drug discovered here in our laboratories, poised to become the first KU-invented cancer drug to go from bench to bedside entirely within the confines of our institution. We also discuss our sharpened focus on the underserved and minority populations, who all too often slip under the radar when it comes to prevention and early detection. Personalized medicine continues to be a vital component to our research. All of these and more demonstrate KU Cancer Center’s commitment to studying cancer from all aspects. A common thread throughout the report is the importance of collaboration across laboratories and institutions, including Stowers Institute for Medical Research and Children’s Mercy. By joining forces, patients benefit from a deeper pool of specialists and clinical trials, and researchers have access to a larger group of subject matter experts
Without our researchers, scientists, clinicians and staff, our progress against cancer would come to a halt, but our team brings new insights and discoveries to the fight against cancer on a daily basis, and I am proud to share their work in this report. It is an honor to be surrounded by such an ambitious and committed group of people, all united in the quest to serve our patients and their families. I hope you enjoy learning more about The University of Kansas Cancer Center. Sincerely, Roy A. Jensen, M.D. Director, The University of Kansas Cancer Center Director, Kansas Masonic Cancer Research Institute
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Beyond the Bench
At The University of Kansas Cancer Center, we look at cancer from several perspectives.
I have been overwhelmed with the support KU Cancer Center has received from the community. Our supporters and donors have unfailingly been our biggest champions. In return, KU Cancer Center employees are giving back to the community, extending contributions beyond lab benches and clinics.
Scott Weir, Pharm.D., Ph.D., John Taylor III, M.D., MS, and Shrikant Anant, Ph.D.
A new hope for bladder cancer patients bladder cancer drug discovered and developed at The University of Kansas Cancer Center is set to become its first cancer drug to go from bench to bedside.
KU Cancer Center’s nationally recognized proof-of-concept center and product development arm, the Institute for Advancing Medical Innovation (IAMI), translates laboratory and bedside discoveries into new drugs, diagnostic tests and medical devices with the goal of advancing promising medical innovations to patients. Simply put, IAMI works with KU Cancer Center and other National Cancer Institutedesignated centers to develop medical innovations that change the standard of cancer care. Through a research effort led by IAMI, patients with bladder cancer may finally have a new treatment option. More than two decades have passed since a new therapy has been introduced. Bladder cancer is the fifth most common cancer in the United States, with approximately 77,000 new cases and 16,000 deaths annually. It has the highest recurrence rate among all cancers – up to 50 percent of cases may recur within 12 months. Additionally, 25 percent may advance to muscle invasive disease, requiring more aggressive treatment. As such, patients face a lifetime of monitoring and medical care. Standard care for non-muscle invasive disease is surgical removal of the tumor and possible administration of chemotherapy or immunotherapy directly into the bladder. While effective for most patients, some cases may not respond, develop intolerance, or recur during treatment.
Giving an old drug a new purpose Ciclopirox was first marketed in 1982 as an antifungal agent found in several topical drug products. KU Cancer Center researchers began working on ciclopirox through a collaboration with The Leukemia and Lymphoma Society and Ontario Cancer Institute as a potential treatment for acute myeloid leukemia (AML). However, a clinical trial demonstrated that ciclopirox, given orally, was not a viable treatment.
Researchers Scott Weir, Pharm.D., Ph.D., director of IAMI, and Shrikant Anant, Ph.D., associate director for cancer prevention and control research program, decided to modify the drug to be administered intravenously. The new drug, called Ciclopirox Prodrug, converted to ciclopirox in the bloodstream where it then was selectively delivered to the urinary tract. Further research demonstrated that it was able to kill bladder cancer cells. Following these promising findings, Anant and Weir recruited renowned bladder cancer expert John Taylor III, M.D., MS, professor of urology at the University of Kansas School of Medicine, whose lab has extensive experience in bladder cancer modeling, as well as the ideal mouse model in which to test the drug. The outcome? “Fantastic results. Not only did the drug have an effect on the cancer cells, but it did not harm surrounding healthy cells,” Anant said. Anant, Taylor and Weir demonstrated in animals that giving Ciclopirox Prodrug by injection selectively delivers the active anticancer agent, ciclopirox, to the entire urinary tract. At well tolerated doses administered intravenously and by injection, urinary tract concentrations of the active agent are achieved that exceed those required to kill bladder cancer cells in the test tube by severalfold. “This is potentially a game-changer in treating patients with non-invasive bladder cancer. A new and effective drug, which doesn’t require catheterization, is welcomed in a field where care has not advanced much in several decades,” Taylor said. Because the Food and Drug Administration (FDA) requires extensive resources to demonstrate that a drug is a viable treatment for patients, academic institutions often partner with the private sector to advance the drug to a clinical trial. Under an existing partnership agreement, the University of Kansas Medical Center licensed Ciclopirox Prodrug to BioNovus Innovations LLS. Development is being managed by BioNovus subsidiary CicloMed LLC. This is the first product development and commercialization collaboration between BioNovus and IAMI. CicloMed is on track to submit an investigational new drug (IND) application to the FDA in early 2017. Pending FDA clearance, the firm intends to initiate a Phase I clinical trial at several sites, including KU Cancer Center. The goal is to enroll the first patient in a clinical trial by mid-2017. “It takes a village to understand the biology of cancer, discover and develop new cancer treatments and demonstrate that the treatment is effective,’ Weir said. “We’re proud to have built a team of experts whose strengths span the spectrum of research – from basic to translational to clinical. Because of this team effort, bladder cancer patients may soon have better treatment options.”
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Beyond the Bench
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Preventing cancer in Latinos, one text message at a time T
he nation’s Latino population has been one of its fastest growing in recent decades, accounting for more than half of total U.S. population growth from 2000 to 2014. This group is expected to reach 106 million in 2050, double what it is today, according to U.S. Census Bureau population projections.
Despite population size, Latinos are an underserved group, experiencing significant disparities in health care including higher rates of particular cancers, lower cancer screening rates and cancer diagnoses at more advanced stages than non-Latinos. Now, consider this: the growth rate in U.S. Latino cancer cases is projected to hit an astounding 142 percent by 2030.
Beyond the Bench
Paula Cupertino, Ph.D., director of the University of Kansas Medical Center’s Juntos Center for Advancing Latino Health, and her bilingual team, which includes researchers from The University of Kansas Cancer Center and Children’s Mercy, are working to reduce this looming health crisis through cancer prevention, and they are doing it in a unique way. Cupertino’s team is connecting Latinos with tobacco cessation treatment (both medication and behavioral support) via text messaging. Why text messaging? Latinos are the fastest users and adopters of cell phones and respond more to the text message market than any other group. Since 2009, Latinos have closed the gap between whites for cell phone ownership – about 86 percent of Latinos own cellphones compared with 84 percent of whites. Eighty-seven percent of Latinos use their phones for texting, whereas only 79 percent of whites text. “Given Latinos preferences towards smartphones, mobile health care is key. Latinos are a critically
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underserved group that falls outside of the traditional health care system. Access to standard face-to-face care can be an issue, but anyone with a cellphone can text and simply access cessation resources,” Cupertino said. Over the last several years, text message programs have been implemented to promote and encourage healthy behaviors. However, when it comes to existing Spanish language tobacco cessation text message programs in the United States, Cupertino’s research team found that these programs are not adapted or tailored to Latinos. To address this need, Cupertino and Edward Ellerbeck, M.D., MPH, co-leader of the cancer control & population health research program, worked with mobile health engagement company Agile Health to create a program that would “speak” to this population. Prior to the study, Agile Health had rolled out a similar text messaging program to its clients – which includes companies such as Walmart – but the program was not gaining traction with the Latino community. Latinos have unique smoking habits, tending to be social smokers who smoke fewer cigarettes than other population groups, and the program needed to be tailored to their usage habits. The team applied for and was awarded a Small Business Technology Transfer (STTR) grant from the National Institutes of Health (NIH), which funds small business and nonprofit research institutions and serves to bridge the gap between basic science and commercialization of the resulting innovations. Now 600 participants in the United States are enrolled in a trial evaluating the effectiveness of a
smoking cessation text messaging program. What’s more, it has sparked international collaborations in two other countries: Mexico, where a smoking cessation program of this kind has never before existed; and Brazil, where more than 20,000 smokers have already adopted this pre-paid program. For the U.S. program, Juntos researcher Mariana Ramirez reports a 33 percent quit rate. By comparison, 2010 data from the National Health Interview Survey shows that only 6.2 percent of all smokers (of all races) quit in a given year. Onehundred percent of the study’s reported quitters have been biologically tested, confirming there is no tobacco in the participant’s system. Participant feedback has been overwhelmingly positive. One commented that if it weren’t for the program, he would have continued smoking. Ramirez attributes its success to Latinos higherthan-average engagement with their cellphones. “It’s encouraging to see how engaged Latinos are with this program. When participants communicate with their counselor via text, they are enjoying a real back-and-forth conversation. These interactions average about 30 texts per day. With other ethnicities, the average is eight text messages,” Ramirez said. Cupertino notes that, given its effectiveness, in terms of both quit-rate and cost, the program has potential for an even greater global reach. “My entire Juntos team is made up of Latino immigrants from countries all over the world – Brazil, Ecuador, Spain, Colombia, Mexico, to name a few,” Cupertino said. “We are passionate about helping Latinos everywhere quit smoking tobacco, one text message at a time.”
Principal Investigators Delwyn Catley, Ph.D., Edward Ellerbeck, M.D., MPH, Paula Cupertino, Ph.D., and Lisa Sanderson Cox, Ph.D.
John Perry, Ph.D., Linheng Li, Ph.D., and Tara Lin, M.D.
Getting to the root of the problem by targeting cancer stem cells hemotherapy treatment targets and kills cancer cells in the body. However, even after treatment, some cancer cells may remain in the patient’s system undetected.
The lingering cancer can sometimes be in the form of cancer stem cells, which have two unique but dangerous characteristics. First, they are able to self-renew or multiply; and second, they can give rise to a large number of differentiated tumor cells. If these cancer stem cells are not destroyed during initial treatment, they survive and can lead to cancer relapse. Tara Lin, M.D., director of the acute leukemia program at The University of Kansas Cancer Center, likens cancer stem cells to hidden weeds in a garden. “If you pull only the visible top part of the weeds, they will always grow back. The same holds true for cancer. If you treat only what is noticeable and obvious, you’re not getting everything – and that’s why the disease can come back. You’re not getting to the roots,” Lin said. A research team comprised of members from KU Cancer Center, Stowers Institute for Medical Research, and Children’s Mercy are looking at ways to target cancer stem cells to ensure that once a cancer patient goes into remission, they are not at risk of their cancer returning. Linheng Li, Ph.D., Stowers Institute investigator and co-leader of KU Cancer Center’s cancer biology research program, and John Perry, Ph.D., Stowers Institute senior research associate, have been studying cancer stem cells in leukemia and colon cancers for years. “In chemotherapy, you’re first killing the active cycling cells, but then the quiescent, or dormant
cancer stem cells survive the treatment and multiply,” explains Li. “It’s these latent cells that may be the cause of cancer relapse. We wanted to find ways to get at these chemo-resistant quiescent cancer stem cells.” The researchers needed a deeper understanding of these stem cells and what factors cause them to self-renew, as well as ways to inhibit regeneration and thus kill them during cancer treatment. “We studied cancer stem cells at both the molecular and cellular levels, including the signals that promote this proliferation, which is critical for cancer stem cell survival and tumor growth. We also took a close look at patient samples, many from Children’s Mercy, to compare and contrast the different variations of cancer to distinguish the types of leukemia that were similar to what we observed from our animal model study,” Perry said. Their basic research project now serves as the basis for a pilot clinical trial at KU Cancer Center. In this project, the team is focusing on patients with certain types of acute leukemia.
From the laboratory to the clinic The research team collaborated with KU Cancer Center’s state-of-the-art high-throughput screening core facility, where thousands of drug compounds were screened. High-throughput screening, an important step in the drug discovery process, is a way of rapidly assessing a large number of potentially active drugs to identify active compounds which control a particular pathway. Screening tests revealed that a chemotherapy drug, daunorubicin, which has been a mainstay cancer
treatment since the 1970s, showed potential in killing cancer stem cells. For patients with certain blood cancers, the drug is typically administered at a very high dose in order to induce DNA damage sufficient to kill cancer cells, which can produce side effects. However, experiments in the laboratory revealed that a much lower dose of daunorubicin can target and specifically kill those lingering cancer stem cells not by inducing DNA damage but by inhibiting the signaling pathway that cancer stem cells depend on to survive. The team has begun testing this hypothesis in the clinic. To test the effectiveness of low-dose daunorubicin on cancer stem cells, in late 2016, the team started enrolling patients with two kinds of acute leukemia - acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Patients will be treated with one week of low-dose daunorubicin intravenously at the KU Clinical Research Center. The medication is given for only a short timeframe so as not to compromise long-term treatment. A bone marrow sample will be taken before treatment and at completion of the therapy to measure the effect of the low-dose daunorubicin on the cancer stem cells. The goal is that the low dose of daunorubicin will specifically target this self-renewal pathway and kill the cancer stem cells. This particular clinical study, which is still ongoing, focuses on AML and ALL. However, the team believes the treatment may be applicable to a variety of other cancers, including solid tumors. “For some patients in remission, the cancer comes back. That’s where a treatment approach like this can really make a difference. We want to get those lingering roots so that a patient can go into remission and stay in remission,” Lin said.
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Beyond the Bench
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The Right Chemistry: Collaborating Across Multiple Disciplines W
hen it comes to collaborating in cancer research, two heads are better than one. In fact, a single study can traverse dozens of different disciplines, requiring many specialists. Steven Soper, Ph.D., a bioanalytical chemist and biomedical engineer, joined the University of Kansas after several years at the University of North Carolina Lineberger Comprehensive Cancer Center. Here, he hopes to bring the same spirit of collaboration he fostered at North Carolina.
“Since joining the KU system, I’ve been looking at generating new collaborations, as well as drawing on existing ones with KU Medical Center, in particular, the Cancer Center,” Soper said. “When it comes to advancing cancer diagnostics and therapies faster and more efficiently, why wouldn’t you pool resources?” Prior to joining KU, Soper tapped Andy Godwin, Ph.D., deputy director of The University of Kansas Cancer Center and director of molecular oncology for KU Medical Center.
Beyond the Bench
“On a visit to Kansas, I had the opportunity to meet with Andy. We found we were united by a common goal: using biomarkers from blood samples that may serve as a foundation for generating innovative diagnostic tools for different types of cancers,” Soper said.
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The combination of Soper’s biomedical engineering background and Godwin’s experience in oncology precision medicine research make for an ideal partnership. Biomedical engineering is a relatively new engineering sub-discipline gaining a lot of attention in the medical research field. In fact, the National Institutes in Health recently established a new institute in which one of its major themes is biomedical engineering.
“Biomedical engineers are here to help physicians, clinicians and biologists. They pose the research questions, and we introduce new tools to help them answer those questions,” Soper said. “It brings an engineer’s perspective to clinical work.” One of the tools that Soper and Godwin are collaborating on is the “lab-on-a-chip,” a testing platform that captures and performs analysis of various biomarkers, which are actively released by tumor cells into blood. Rather than the usual invasive and costly biopsy, the credit-card size devices will screen for circulating markers that are released from cancer cells within patients’ blood. Extracellular vesicles, or exosomes, for example, are rich with information. No more than about one-thousandth of a human hair’s width, exosomes accumulate in the blood and other body fluids of cancer patients and can provide information early in the evolution of a cancer disease. “Cells have their own miniaturized postal service in the form of these vesicles. Exosomes released from cancer cells carry molecular cargo that can be received by surrounding cells and promote signals to help the tumor grow and spread,” Godwin said. “These extracellular vesicles are full of biomarkers, including RNAs and biologically active proteins, which can be used to detect the presence of cancer early and track the disease state during treatment.” In addition to increased efficiency and reduced cost, lab-on-a-chip devices offer unique capabilities that currently can’t be performed in the lab. As another example, Soper and Godwin are working on isolating cancer tumor cells from whole blood. In just one cubic centimeter of whole blood, there are 1 billion red blood cells, 1 million white blood cells and one to 10 cancer cells.
“Our technology extracts these rare tumor cells from blood. This has provided opportunities for clinicians and cancer biologists to understand cancer metastasis, uncover new mutations and guide therapeutic decisions,” Soper said. Godwin added that the lab-on-a-chip helps advance precision medicine, an emerging approach in which disease treatment and prevention are tailored to an individual’s genes, environment and lifestyle. Before precision medicine, most treatments were not personalized, i.e., the one-size-fits-all approach. “The findings from a lab-on-a-chip screening allow us to hone in on the right therapy for a particular patient,” Godwin said. Several of the instruments Soper and his team have developed, once taken through the developmental cycle, will be transitioned to more labs at KU Cancer Center, allowing researchers to take advantage of the latest technology. “This will not only benefit the various research projects going on across KU Medical Center, but will also advance clinical validation of the technology, which in turn helps us obtain FDA clearance to move these technologies into the clinical lab to help patients,” Soper said. When it comes to collaborating for the benefit of cancer research, reaching across different laboratories and institutions helps propel that critical research forward. More often than not, collaborations are not just an opportunity, but a necessity. “The synergy is important because a single researcher can’t do it alone. In a world where more and more tools and resources are available, we want to make sure we are capitalizing on them all,” Soper said.
Steven Soper, Ph.D., and Andrew Godwin, Ph.D.
Susan Abdel-Rahman, Pharm.D., and J. Steven Leeder, Pharm.D., Ph.D.
Getting the dose “just right” aking a cue from the classic fairy tale, Goldilocks and the Three Bears, a team at Children’s Mercy is focused on finding medication doses that are “just right” for each and every patient. The initiative, called GOLDILOKS (Genomic and Ontogeny-Linked Dose Individualization and cLinical Optimization for KidS), looks to better understand patient’s unique characteristics and how they may influence an individual’s response to a medication or treatment. And they’re starting with children, who are often incorrectly viewed as miniature adults when it comes to dosing. J. Steven Leeder, Pharm.D., Ph.D., division director of clinical pharmacology, toxicology and therapeutic innovation at Children’s Mercy believes there is a better approach to ensuring children get the right dose. “There are several factors that contribute to how children respond to medications. You can give a group of kids the same dose of medication and find that the amount of drug in the system – which is what we call ‘exposure’ – varies widely,” Leeder said. Case-in-point, in a Children’s Mercy study, children were given roughly the same weightbased dose of ADHD medication. Findings revealed that the difference between the patient who had the highest exposure compared to the patient with the lowest exposure was fifty-fold. This variability can make the difference between side effects or a failure to respond to treatment. With childhood cancer medications, the stakes are higher. There must be enough medication to kill the cancer, but not so much that it results in severe, irreversible side effects. Understanding patient “exposure” becomes necessary.
What makes a patient respond so differently to a proven treatment? One factor can be a genetic variation, or differences in the DNA sequence in each of our genomes. For example, our bodies contain a specific gene pathway primarily expressed in the liver, which helps eliminate foreign chemicals, including those contained in certain medications. Seven percent of the Caucasian population is genetically deficient in this pathway, and this can affect how a patient responds to treatment. “Many people go their entire life without being aware of this deficiency,” Leeder noted. “But if you are genetically deficient, and you’re prescribed a medication that’s dependent on this pathway for its elimination, a typical dose can lead to an overdose.” To hone in on the correct dose, providers must be aware of each patient’s unique characteristics, including their genomic makeup and age. Children’s Mercy is the first to develop a computerbased medication dosing decision support tool for point-of-care physicians embedded in the patient’s electronic medical record. Susan Abdel-Rahman, Pharm.D., section chief for therapeutic innovation at Children’s Mercy, built the tool for the program’s first drug, Busulfan, a chemotherapy agent with significant patient exposure variability. Multiple doses of Busulfan are given over a fourday period to prepare a child for a bone marrow transplant. Not enough of the medication can lead to transplant rejection, too much can lead to liver failure or even death. “With four clicks, the clinician can visualize what’s going on with each patient and explore the dose
required to get them to where they want the patient to be, then the software returns a dosing recommendation,” Abdel-Rahman said. Most hospitals send the patient’s blood for analysis to an outside laboratory. Often, these labs only operate on weekdays, delaying results. The software, on the other hand, is accessible around-the-clock, pulls in data for analysis and returns a clinical decision to the patient’s record. A mathematical algorithm functions behind the scenes, allowing the physician to simulate a dose, while red-yellow-green tachometers point toward the ideal decision. “Recently, we had a patient who received their dose at 6 a.m. We drew blood levels mid-morning and changed their dose that evening. Rather than sending levels out for analysis – which would delay care by 48 hours – we were able to make a same-day decision,” Abdel-Rahman said. The software is in the works to be adapted by The University of Kansas Cancer Center’s Bone Marrow Transplant program. “It’s exciting to think that this cutting-edge decision support tool may soon be available to our clinicians,” Roy Jensen, M.D., director of KU Cancer Center, said. “This is a great example of our two institutions partnering to give patients the best possible care.” The decision support tool has the potential to make more efficient use of a clinician’s time, return therapeutic decisions more quickly, ultimately impacting care. “What we’re doing is state-of-the-art,” Abdel Rahman said. “Clinicians can make a decision and see the implications before they ever put the dose in the child.”
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Beyond the Bench
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Transforming Cancer Care In our region Y
ears ago, when Drue Jennings’ first wife was diagnosed with cancer, they had no choice but to leave Kansas City for her cancer treatment.
“At the time, there were no area oncologists who could treat her advanced cancer. For years, we commuted to Texas for treatment,” Jennings, former chairman and CEO of Kansas City Power & Light, said. “While in Texas, I was so impressed that there was a public hospital, accessible to anyone nearby. Anyone could walk in and receive world-class treatment. I thought to myself, Kansas City should be able to do this.” It was Jennings experience and others that helped catalyze the call for a robust cancer center in Kansas City. Jennings, along with local philanthropists Bill Hall, of the Hall Family Foundation, and Charlie Sunderland, of the Sunderland Family Fund, were early champions of The University of Kansas Cancer Center. Interestingly, both Hall and Sunderland have also been personally affected by this terrible disease. Like Jennings, Hall had to go outside of Kansas City for his bone marrow transplant. “Kansas City just didn’t have the services at the time,” Hall said. “Of course, now, we have one of the largest bone marrow transplant centers in the world,” he added. Sunderland, too, required a stem cell transplant. “I could’ve gone anywhere, but I was confident in the program and chose to be treated at KU,” he said. The Hall Family Foundation and Sunderland Family Fund’s latest contribution is the newly established medical oncology professorship at KU Cancer Center. The professorship was created through a $1.3 million challenge grant from the Hall Family Foundation and met by a $650,000 donation from the Sunderland Family Fund. They chose to name the professorship the A. Drue Jennings Professorship in Medical Oncology to honor their longtime friend. The gift will support the salary, travel and associated costs for the professorship, which will be at KU Cancer Center and in the Department of Internal Medicine at the University of Kansas Medical Center.
Beyond the Bench
“You invest in people. And Dr. Jensen, the center’s director, was one of the best investments we have ever made. But we can’t stop there. We need to continue hiring the best talent,” Hall said. Sunderland and Jennings, with significant support from the Hall Family Foundation, helped KU Cancer Center obtain prestigious National Cancer Institute (NCI) designation in 2012. The professorship is another step forward in KU Cancer Center’s pursuit of NCI Comprehensive Cancer Center designation. “Moving toward Comprehensive designation is challenging, and Dr. Jensen needs the right
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resources to hire the right people. This opportunity helps him and the Cancer Center,” Sunderland said. Sunderland, who was approached by Jennings to discuss the challenge grant, said it was an easy decision to answer the Hall Family Foundation’s challenge. “We sat down to lunch and Drue explained to me how vital this professorship was to the KU Cancer team. My decision was made by the end of the meal,” he said. Hall, Jennings and Sunderland agree that KU Cancer Center’s impact – to patients, families, the scientific community and the economy – has been far-reaching. “Due to the incredible leadership of Dr. Jensen and the national recognition that comes from being an NCIdesignated center, every aspect of the center – including The University of Kansas Hospital and KU Medical Center – has been elevated over the last several years,” Jennings said. Jennings noted that NCI designation has created a ripple effect for the greater Kansas City area’s economy. The cancer center alone accounts for nearly $3.5 billion in economic impact, including more than 3,300 jobs created since 2007. Still, access to high-quality cancer care, including preventive medicine, rural outreach and early detection, Hall said, is the greatest contribution the center has made to the community. “At the end of the day, providing world-class care in Kansas City is the single most important issue,” Hall said. “There’s somebody out there who is going to be saved because of this institution.” Jennings notes that the cancer care available to Kansas Citians today has significantly improved. Now, Kansas and Missouri families affected by cancer don’t have to add to the stress of treatment by having to travel a great distance. “There’s no reason for any cancer patient to leave Kansas City. The level of care, combined with cutting-edge research, has been transformational to this community,” Jennings said.
Drue Jennings, Charlie Sunderland and Bill Hall
Awards and recognition
Cancer Biology Research Identified as Significant to the Field by Faculty 1000
Jensen Joins Association of American Cancer Institute’s Leadership
Fabian Inducted into KU Women’s Hall of Fame
Kristi Neufeld, Ph.D., KU Cancer Center’s cancer biology program co-leader and professor of molecular biosciences, authored an article entitled, “Human cancer xenografts in outbred nude mice can be confounded by polymorphisms in a modifier of tumorigenesis,” which was recommended for its special significance in F1000Prime by Kent Hunter, F1000 faculty member and deputy chief of the Laboratory of Cancer Biology and Genetics at the National Cancer Institute. F1000Prime is a collection of over 145,000 recommendations of the top articles in biology and medicine. The journal’s faculty includes heads of faculty, section heads and more than 8,000 leading experts in biology and medicine, including Nobel Laureates, Lasker Award winners and Fellows of the Royal Society. One of the study authors, Derek Jensen, was supported in part by the KU Cancer Center Student Summer Research Training Program.
KU Cancer Center Director Roy A. Jensen, M.D., was elected vice president/president-elect of the Association of American Cancer Institutes (AACI). Jensen’s term as vice president began Oct. 2016. Jensen has been a member of AACI’s board of directors since Oct. 2013. As president, Jensen will work with AACI leaders to support the organizational mission of enhancing the impact of academic cancer centers. AACI is comprised of 95 leading cancer research centers in North America, including KU Cancer Center. The association is dedicated to promoting leading research institutions’ efforts to eradicate cancer through a comprehensive and multidisciplinary program of cancer research, treatment, patient care, prevention, education and community outreach. Jensen became the director of KU Cancer Center in 2004, and under his leadership, the center acheived NCI designation in 2012.
Carol Fabian, M.D., associate director of clinical research and director of the Breast Cancer Prevention and Survivorship Research Center at KU Cancer Center, was inducted into the University of Kansas Women’s Hall of Fame, sponsored by the Emily Taylor Center for Women & Gender Equity and the Commission on the Status of Women. This honor is given to women who have accomplished extraordinary feats in their respective fields. Fabian is a nationally recognized medical oncologist and a pioneer in the field of breast cancer research. Her combined focus on breast cancer prevention and biomarker development led to a method that helps women determine if they are at increased risk for breast cancer. She has 30 years of experience in conducting breast cancer research, and has had continuous funding from the National Cancer Institute for performance of clinical research trials for more than 20 years.
Awards and recognition Befort receives KU Scholarly Achievement Award Cancer control and population health program co-leader Christie Befort, Ph.D., was one of five recipients of the University of Kansas Scholarly Achievement Award, which recognizes significant scholarly or research achievement for scholars in the middle of their careers. Befort has developed a reputation for her work in obesity and how it relates to cancer and cancer prevention. She has completed more than 20 research grants as a principal investigator or as a co-investigator, including a $10 million award from the Patient-Centered Outcomes Research Institute (PCORI) in 2014 evaluating three different approaches for treating obesity in primary care settings.
woman faculty member who has demonstrated outstanding leadership and mentoring while encouraging, inspiring and rewarding other female faculty in their academic careers. In this role, Richter will serve as a member of the Women in Medicine and Science (WIMS) Executive Council and develop programs in collaboration with WIMS. Richter is one of only four McCann Professors in the United States.
Women in Medicine and Science Honor Lewis-Wambi with Rising Star Award Joan Lewis-Wambi, Ph.D., assistant professor in the Department of Cancer Biology, is the recipient of the University of Kansas Women in Medicine & Science (WIMS) Rising Star Award. Her research focuses on elucidating the mechanism of endocrine resistance in breast cancer. WIMS honors distinguished women and men at KU Medical Center who have exhibited remarkable support for the advancement of women faculty members’ careers in medicine, nursing and health professions. The Rising Star award recognizes women faculty or non-faculty members in the early phase of their careers.
The American Cancer Society selected Rebecca J. Wates, Ph.D., for a post-doctoral fellowship grant to pursue her research in ovarian cancer. Wates, who works in the lab of KU Cancer Center’s director of molecular oncology, Andrew Godwin, Ph.D., is the first early-career cancer scientist the society has ever supported via crowdfunding. The American Cancer Society supports about 800 investigators nationwide and uses crowdfunding and social media as a way to engage millenials by increasing awareness of the importance of cancer research.
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Beyond the Bench
Richter named Joy McCann Professor at KU Medical Center Wates receives crowdfunded grant Kimber Richter, Ph.D., MPH, member of cancer control and population health program, professor in preventive medicine and public health, has been from American named the 2016-2019 Joy McCann Professor for KU Medical Center. The Cancer Society Joy McCann Professorship is awarded every three years to an accomplished
Key Recruits and Faculty Appointments
Tom Curran, Ph.D., FRS, was named chief scientific officer and executive director of Children’s Mercy Children’s Research Institute earlier this year. The Children’s Research Institute located at Children’s Mercy Kansas City, was established last year to build on the hospital’s century-long history in pediatric research and to focus the hospital’s future research efforts in four key areas: pediatric genomic medicine, clinical pharmacology, health services and outcomes and health care delivery.
John A. Taylor III, M.D., MS, was named professor and director of basic urologic research at the University of Kansas Medical Center. Taylor is a nationally recognized urologic oncologist with a clinical and research focus on bladder cancer.
Curran is a Fellow of the American Association for the Advancement of Science, the American Academy of Microbiology, the Royal Society, London, the Academy of the American Association for Cancer Research, and a member of the Institute of Medicine of the National Academies, USA, and the American Academy of Arts and Sciences. He served on the National Cancer Institute Board of Scientific Advisors from 2000 to 2005 and is a past president of the American Association for Cancer Research.
Following his residency at Columbia University, Taylor served three years on active duty at Walter Reed Army Medical Center. Prior to joining KU Cancer Center, he was a professor at the University of Connecticut Health Center.
Curran’s research interests have spanned the areas of molecular biology, cancer research and neurobiology. Currently, his laboratory is focused on pediatric brain tumors, brain development and genomics, concentrating on the goal of finding new treatments for childhood brain tumors. He has published more than 290 research articles that have been cited more than 50,000 times. Curran is truly a world-class scientist who will play a critically important role in building the depth and breadth of pediatric cancer research at KU Cancer Center and is a key addition to our leadership team.
Taylor is a member of the Bladder Cancer Research Network Management Committee and a Scientific Advisory Board member for the Bladder Cancer Advocacy Network. He is also a member of the National Cancer Institute’s Bladder Cancer Task Force for Clinical Trial Development.
Key Recruits and Faculty Appointments Sally Maliski, RN, Ph.D., FAAN, was named associate director for Health Equity and dean of the University of Kansas School of Nursing. Maliski oversees KU Cancer Center’s cancer disparities and health equity research and outreach efforts. Maliski’s research focus is on symptom experience and management among low-income populations, primarily focusing on men with prostate cancer and their families.
Allen Chen, M.D., was recruited and appointed as the Joe and Jean Brandmeyer Chair of the Department of Radiation Oncology at the University of Kansas School of Medicine. Chen is internationally renowned for his research in the treatment of head and neck cancers and is the principal investigator for several clinical trials combining chemotherapy with radiation.
Steven Soper, Ph.D., joined the University of Kansas as one of 12 Foundation Distinguished Professors. He is the 10th Foundation Professor named to date. Soper is a leading international researcher in developing new technologies that have applications for disease detection. Soper’s research largely focuses on the development of tools to isolate circulating tumor cells, as well as the development of nanoscale devices for nextgeneration sequencing.
Joseph McGuirk, D.O., KU Cancer Center’s medical director for the blood & marrow transplant program, was named the Schutte/Speas Professor of Hematology/Oncology.
Soper’s awards and honors include fellow status in the American Association for the Advancement of Science, the Royal Society of Chemistry and the Society for Applied Spectroscopy; the ACS Award in Advances in Chemical Instrumentation; the A.A. Benedetti-Pilcher International Microchemical Award; the Whitaker Foundation Award; the National Institutes of Health Shannon Award; and the R&D 100 Award. He has been awarded roughly $57 million in research funding.
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Beyond the Bench
Carol Fabian, M.D., previously co-leader of the cancer prevention and survivorship program, was promoted to associate director for clinical research.
Public Policy and Advocacy Indoor Tanning Law
HPV Vaccinations
Tobacco Use
People who use tanning devices before age 35 have a 59 percent greater risk of being diagnosed with melanoma. In collaboration with the American Cancer Society, KU Cancer Center developed, advocated for and obtained passage of the Kansas Tanning Facilities Act, which prohibits anyone under 18 years of age from using a tanning facility.
Every 20 minutes, someone in the United States is diagnosed with an HPV-related cancer. In 2013, Kansas had the lowest HPV vaccination rate in the nation. KU Cancer Center developed a comprehensive response to address this critical issue. In 2015, over 50 percent of Kansas girls had at least one HPV vaccination, an increase from 38 percent in 2014.
KU Cancer Center supports the Tobacco 21| KC initiative, which seeks to raise the age requirement to purchase tobacco products from 18 to 21. So far, that ordinance has passed in 21 municipalities throughout greater Kansas City, impacting 1.4 million people.
Tobacco 21 Cities State Indoor Tanning Restrictions for Minors Younger than 18 Years, as of June 2016
At Least One Dose HPV Vaccination Among Females Aged 13-17
WA MT
ME
VT
ND MN
OR ID
NH WI
SD
NY
NV
PA
IA
NE
IL
UT CO
CA
IN
OH WV
KS
KY
MO
OK
NM
AR
SC MS
TX
VA NC
TN AZ
MA
MI
WY
AL
GA
NJ DE MD DC
70 60 50
LA
AK
CT
RI
FL
62.8%
60% 38.3%
30 HI
ORDINANCE PASSED ACTIVE DISCUSSIONS
50.9%
40
20
Prohibits all minors under 18 from tanning
Parental permissions or accompaniment only
Prohibits some minors from tanning
No restrictions for minors
Prohibits all minors under 18 from tanning Prohibits some minors from tanning Parental permission or accompaniment only No restrictions for minors
10 As of December 2016
0
2014 United States
2015 Kansas
Source: Immunize Kansas Coalition
Adopted Cities Kansas City, MO Leavenworth, KS Lansing, KS Overland Park, KS Leawood, KS Bonner Springs, KS Kansas City, KS Liberty, MO Roeland Park, KS Olathe, KS Gladstone, MO Iola, KS Independence, MO Grandview, MO Mission Hills, KS Lee’s Summit, MO Prairie Village, KS Westwood, KS Lenexa, MO Uninc. Jackson Co. MO Westwood Hills, KS Total Population - 1,420,598
High-Impact Publications
Park JW, Liu MC, Yee D, Yau C, van ‘t Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA. Adaptive Randomization of Neratinib in Early Breast Cancer. The New England journal of medicine. 2016;375(1):11-22. Epub 2016/07/15. doi: 10.1056/NEJMoa1513750. PubMed PMID: 27406346. Rugo HS, Olopade OI, DeMichele A, Yau C, van ‘t Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ. Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. The New England journal of medicine. 2016;375(1):23-34. Epub 2016/07/15. doi: 10.1056/ NEJMoa1513749. PubMed PMID: 27406347. Qian P, He XC, Paulson A, Li Z, Tao F, Perry JM, Guo F, Zhao M, Zhi L, Venkatraman A, Haug JS, Parmely T, Li H, Dobrowsky RT, Ding WX, Kono T, FergusonSmith AC, Li L. The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism. Cell stem cell. 2016;18(2):21428. Epub 2015/12/03. doi: 10.1016/j.stem.2015.11.001. PubMed PMID: 26627594.
Fabian CJ, Meyskens FL, Jr., Bajorin DF, George TJ, Jr., Jeter JM, Khan S, Tyne CA, William WN, Jr. Barriers to a Career Focus in Cancer Prevention: A Report and Initial Recommendations From the American Society of Clinical Oncology Cancer Prevention Workforce Pipeline Work Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016;34(2):186-93. Epub 2015/11/04. doi: 10.1200/jco.2015.63.5979. PubMed PMID: 26527778. Sharma P, Bergman JJ, Goda K, Kato M, Messmann H, Alsop BR, Gupta N, Vennalaganti P, Hall M, Konda V, Koons A, Penner O, Goldblum JR, Waxman I. Development and Validation of a Classification System to Identify High-Grade Dysplasia and Esophageal Adenocarcinoma in Barrett’s Esophagus Using NarrowBand Imaging. Gastroenterology. 2016;150(3):591-8. Epub 2015/12/03. doi: 10.1053/j.gastro.2015.11.037. PubMed PMID: 26627609. Hamilton-Reeves JM, Bechtel MD, Hand LK, Schleper A, Yankee TM, Chalise P, Lee EK, Mirza M, Wyre H, Griffin J, Holzbeierlein JM. Effects of Immunonutrition for Cystectomy on Immune Response and Infection Rates: A Pilot Randomized Controlled Clinical Trial. Eur Urol. 2016;69(3):389-92. Epub 2015/12/15. doi: 10.1016/j. eururo.2015.11.019. PubMed PMID: 26654125; PMCID: PMC4793712. Maxson JE, Ries RE, Wang YC, Gerbing RB, Kolb EA, Thompson SL, Guidry Auvil JM, Marra MA, Ma Y, Zong Z, Mungall AJ, Moore R, Long W, Gesuwan P, Davidsen TM, Hermida LC, Hughes SB, Farrar JE, Radich JP, Smith MA, Gerhard DS, Gamis AS, Alonzo TA, Meshinchi S. CSF3R mutations have a high degree of overlap with CEBPA mutations in pediatric AML. Blood. 2016. doi: 10.1182/ blood-2016-04-709899. PubMed PMID: 27143256.
Yoshida MM, Ting L, Gygi SP, Azuma Y. SUMOylation of DNA topoisomerase IIalpha regulates histone H3 kinase Haspin and H3 phosphorylation in mitosis. The Journal of cell biology. 2016;213(6):665-78. Epub 2016/06/22. doi: 10.1083/jcb.201511079. PubMed PMID: 27325792; PMCID: PMC4915188. Pinto CS, Raman A, Reif GA, Magenheimer BS, White C, Calvet JP, Wallace DP. Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney Disease. Journal of the American Society of Nephrology : JASN. 2016;27(4):1124-34. Epub 2015/08/21. doi: 10.1681/ asn.2015010047. PubMed PMID: 26289612; PMCID: PMC4814181. Cooper TM, Cassar J, Eckroth E, Malvar J, Sposto R, Gaynon P, Chang BH, Gore L, August K, Pollard JA, Dubois SG, Silverman LB, Oesterheld J, Gammon G, Magoon D, Annesley CE, Brown PA. A Phase I Study of Quizartinib Combined With Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016. Epub 2016/02/28. doi: 10.1158/1078-0432.ccr-15-1998. PubMed PMID: 26920889. Sharma P, Lopez-Tarruella S, Garcia-Saenz JA, Ward C, Connor C, Gomez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell A, Del Monte-Millan M, GonzalezRivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, Gonzalez Del Val R, Cortes J, Fuentes Rivera H, Bretel Morales D, Marquez-Rodas I, Perou CM, Wagner J, Mammen JM, McGinness M, Klemp JR, Amin A, Fabian CJ, Heldstab J, Godwin AK, Jensen RA, Kimler BF, Khan QJ, Martin M. Efficacy of neoadjuvant carboplatin plus docetaxel in triple negative breast cancer: Combined analysis of two cohorts. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016. Epub 2016/06/16. doi: 10.1158/1078-0432.ccr-16-0162. PubMed PMID: 27301700.
21
Beyond the Bench
Parrales A, Ranjan A, Iyer SV, Padhye S, Weir SJ, Roy A, Iwakuma T. DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. Nature Cell Biology 2016 Nov;18(11):1233-1243. doi: 10.1038/ ncb3427. Epub 2016 Oct 24. DOI: 10.1038/ncb3427. PubMed PMID: 27775703.
Giving back to the community J
ust as important as the work we do in the laboratory, our employees are out in the community, engaging in meaningful partnerships to help spread cancer awareness. Every year, KU Cancer Center employees attend dozens of events to staff cancer awareness run/walks, support organization fundraisers and facilitate cancer screenings. KU Cancer Center wouldn’t be here without the support of our community, and we strive to support the community in return. ď ľ
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Beyond the Bench
Giving back to the community
Mail Stop 1027 | 3901 Rainbow Boulevard Kansas City, KS 66160
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