THE DRUG DISCOVERY BUILDING

Discovering Cures, Imagine trying to put a jigsaw puzzle together with the pieces in different rooms. Now consider how much faster the process would be if the pieces were brought together first. That’s the analogy used by Dr. Charles Smith, the Charles and Carol Cooper Endowed Chair in Pharmacy and SmartState Endowed Chair to explain the significance of MUSC’s 114,000-square-foot Drug Discovery Building. Holder of many American and international patents, he was recruited to MUSC from Penn State University to direct the Drug Discovery Core. Smith is an expert in high throughput screening. He designs new drugs to fight cancer by unlocking molecular mechanisms important for preventing tumor growth. Smith believes the new building, which bundles research labs together, will heighten creative collaboration and productivity. “The new building will help integrate the whole process of drug discovery and development. Proximity helps to generate collaboration, and the new building brings together multiple disciplines,” said Smith. This coordination is essential, given the lengthy process of drug discovery. For example, it takes more than $800 million and 15 years to bring a new drug to market, and fewer are making it despite advances in understanding diseases processes.

Drug discovery is an expensive, lengthy and fragile process.

Target Discovery

Chemical Library Screening

Lead Optimized

Pre-clinical Studies

Clinical Trials

15 years and $800 million from target to product

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Market Entry

Driving the Economy Private industry, driven by investors’ need for larger returns on guaranteed winners, has increasingly turned to lifecycle management of existing products rather than early-stage discovery. This opens up an opportunity for academic researchers to drive the early, more innovative steps in drug discovery. Nevertheless, academic institutions often lack the resources and infrastructure needed to conduct high-risk, high-reward drug discovery research that could lead to the next breakthrough. Despite this intimidating environment for discovery, business and education leaders in South Carolina point to biomedical research as a potential economic powerhouse for the state. Enter the Drug Discovery Building, part of the James E. Clyburn Research Center, as a way to fill the gap. The building is situated on the MUSC campus, but the scientists within it represent direct collaboration among MUSC, Clemson University and the University of South Carolina, as well as existing and new partnerships with the private sector. Dr. Rick Schnellmann, Chair of the Department of Pharmaceutical and Biomedical Sciences at the South Carolina College of Pharmacy, believes that innovative drug discovery has to be a collaborative process. “The most effective way to move from academic research to an FDA-approved product that can help a patient is through partnerships between the academic and private sectors,” said Schnellmann.

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“The discovery of successful, improved agents for the treatment of cancer would have a significant impact on the lives of patients in South Carolina and beyond.”

“On our end, we need the right basic scientists in place to drive the research to the point that will appeal to private industry for further development, which will get the drugs patients need into the market,” added Schnellmann. The Drug Discovery Building plays a big part in getting the right basic scientists in place. The state’s investment in the Centers of Economic Excellence, designed to draw the nation’s top scientists to the state as SmartState Endowed Chairs, is paying off in part because of the promise MUSC’s investment in drug discovery

Dr. Patrick Woster

represented for candidates. Dr. Patrick Woster is a prime example. Woster, a SmartState Endowed Chair in Drug Discovery and Professor of Pharmaceutical and Biomedical Sciences, arrived in 2011, bringing a much-needed specialization to the drug discovery process. He is an expert in medicinal chemistry focusing on changing the molecular structure of potential drugs to optimize therapeutic value. “I was drawn to my position by the reputation of MUSC as an emerging power in biomedical research, and by the numerous opportunities to conduct collaborative research aimed at the discovery and development of new therapeutic agents,” said Woster. There are several cores and research foci represented in the new building, which will take advantage of the pooled expertise in drug discovery and state-of-the-art technologies. 20

In many ways, Smith and Dr. Andrew Kraft, Director of Hollings Cancer Center at MUSC and Dr. William H. Folk Chair in Experimental Oncology, exemplify what the new Drug Discovery Building makes possible. Kraft is a medical oncologist and nationally recognized researcher who led the Hollings Cancer Center to become a National Cancer Institute-designated cancer center. The Hollings Cancer Center is one of just 66 in the U.S., and the only center in South Carolina, to hold that designation from the National Cancer Institute. This distinction is awarded only to those centers conducting the most advanced research and clinical trials. Smith and Kraft collaborated on research into inhibitors of Pim protein kinases, which play a significant role in the development of T cell lymphomas and prostate cancer. They screened a library of 50,000 chemicals for novel Pim-1 inhibitors, eventually identifying compounds that effectively inhibit the kinase, which could lead to novel anticancer drugs. The potential impact of this discovery on patients is significant. Very few compounds have been identified as Pim inhibitors, and those that have are poorly selective, leading to non-specific toxicity and lack of clinical utility. A company founded by Smith, called Apogee Biotechnology Corporation, took a similar approach to developing inhibitors of an enzyme known as sphingosine kinase. The compound in that program recently entered Phase I clinical testing in cancer patients at the Hollings Cancer Center. MUSC is the lead institution for testing this new anticancer drug candidate. Drug discovery is one mechanism for economic development. High tech, medically-focused technology is increasingly important as we try to develop safer and more effective drugs for many diseases. Building many new small companies to create a biotech cluster in Charleston could have a significant economic impact. 21

GOING THE DISTANCE As recently as 30 years ago, a diagnosis of cancer represented a grim prognosis for most patients. There were so few drugs available that treatment took a one-size-fits-all approach, and researchers knew very little about how cancer developed and spread, and more important, how it could be stopped. Thanks to advances in research and treatment, today the outlook for cancer patients is significantly better. Even though cancer remains the second leading cause of death in the U.S., trailing only after heart disease, millions of people are recovering from the disease. Significant discoveries don’t happen in isolation. Rather, they are the result of collaboration and building upon the work of like-minded researchers across generations and geographic boundaries. The work at the Clyburn Research Center is a perfect example. “Cancer isn’t one disease, it is many diseases,” said Dr. Dennis Watson, a molecular biologist with Hollings Cancer Center who has been on the cutting-edge of cancer research for decades. “The good news is that we have many more tools to study it. We’ll make more progress against cancer in the next 10 years than we have in the last 50.” Watson leads the Cancer Genetics and Molecular Regulation program, one of three cancer research programs located in the Clyburn Research Center. The others are the Developmental Cancer Therapeutics and the Cancer Prevention and Control programs. Watson’s lab, located in the Bioengineering Building, focuses on two main areas of research: how genes regulate cellular functions; and how certain genes trigger the growth, development and spread of specific types of cancer.

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His research suggests that the absence of a specific gene called PDEF may play a critical role in triggering the growth and spread of breast, colon and prostate cancers. Conversely, a re-expression of it can inhibit those functions. At a more basic level, Watson said they’re working to determine what makes cancer destructive and what makes it spread. They’re also working to differentiate specific disease types so each patient’s case can be treated with the most appropriate therapy. “Prostate cancer is a good example. Only about 20 percent of prostate cancer types are invasive enough to cause serious morbidity and mortality. Knowing the specific type involved is critical to both selecting the right treatment and avoiding unnecessary surgery and therapies for the patients who don’t need them,” said Watson. The research conducted within the Cancer Prevention and Control Program targets risk factor identification, prevention and survivorship, while also considering issues such as tobacco control and cancer disparities among the rural, poor and minority populations in South Carolina. In the Developmental Cancer Therapeutics Program, housed in the Drug Discovery Building, researchers work to develop drugs that can target specific cancers more directly and with fewer side effects. Dr. Patrick Woster, SmartState Endowed Chair in Medicinal Chemistry, said the discovery of successful, improved agents for the treatment of cancer would have a significant impact on the lives of patients in South Carolina and beyond.

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“We hope to increase the scope of our research efforts to include many aspects of the drug development process, ultimately leading to human clinical trials,” said Woster. Hollings Cancer Center Director Dr. Andrew Kraft agrees. Professionally, he came of age in the 1970s when drug discovery in cancer research was at an early stage. Researchers had only recently discovered the first genes involved in cancer and were just beginning to understand the disease’s molecular basis. Kraft has seen dramatic changes in the treatment of cancer. As both a physician and a cancer researcher, he knows what a difference basic discoveries made in the laboratory can mean for the patient. “Every new piece of knowledge, new discovery or therapy advances our understanding of disease and how to prevent or cure it, but it’s a slow process,” said Kraft. “It took years, but diseases such as polio have been eradicated because people stayed the course and kept looking for answers. If we stay the course, we can make a difference.” Kraft understands that patients have many questions and need answers now. “They want to know why some people are at greater risk for cancer, how it might be prevented and how they might benefit from a drug with fewer side effects. And, the question at the top of the list – is there a cure for the kind of cancer they have?”

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At the Clyburn Research Center, the best of the best are working together to find the answers. Dr. Ken Tew, Professor and Chairman of the Department of Cell and Molecular Pharmacology and Experimental Therapeutics, and the John C. West SmartState Chair of Cancer Research, recognizes the importance of continuing the search for cures. “As a species, we need to push the envelope, to keep hope alive and find solutions,” said Tew. He and his colleagues study the chemical reactions within cells to decipher the difference between tumor cells and normal cells. Tew says that MUSC now has a critical mass of experts in these fields interacting with each other, sharing knowledge and creating new opportunities with far-reaching potential. In the final analysis it is perseverance and collaboration that will lead to promising breakthroughs. “You can’t isolate yourself,” said Kraft. “The experts in areas outside your own discipline offer new perspectives that advance the possibilities and bring you closer to a solution. There is a winning strategy. We will not give up.”

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“There is a winning strategy. We will not give up.” Dr. Andrew Kraft

CANCER PREVENTION AND CONTROL A conversation about making a difference for South Carolina

What is your program and how is it making a difference for South Carolinians? Our program is called the Cancer Prevention and Control Program. It is one of five research programs within South Carolina’s only National Cancer Institute-designated center, Hollings Cancer Center. On the prevention side, we work to better understand what causes cancer in human beings, and hopefully, to develop new strategies that would prevent cancer from ever occurring in individuals. On the cancer control side, we work to develop strategies to enhance the lives of cancer survivors. How do you prevent cancer from happening? We know that cigarette smoking causes one-third of all cancer deaths. Any steps we can take to prevent the uptake of smoking in childhood and to promote cessation among smokers is a sure-fire way to prevent cancer. This is why a centerpiece of our program is tobacco control. Another area of great interest is chemoprevention. Dr. Mike Wargovich, Director Dr. Anthony Alberg Associate Director, Cancer Prevention and Control

of Cancer Chemoprevention, is looking for naturally occurring or synthetic products that prevent the occurrence of cancer. Even when cancer is not prevented from occurring, deaths can be prevented by looking for better ways to detect the disease in its early, more curable stages. Are there some cancers that could become eradicated? Yes. There’s an area on the prevention side that translates discoveries into the population. For example, we now live in an era where cervical cancer could theoretically become a disease of the past with the development of human papilloma virus vaccines.

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Researchers in our program are focusing on understanding the perception and misperceptions of cervical cancer, of vaccines in general and of human papilloma virus vaccine in particular. Our hope is to develop educational interventions that might overcome some of the misperceptions that surround the disease. Are there important cancer health disparities? Yes, and the most important disparity is that African Americans suffer from a disproportionate share of the cancer burden, and we live in a state that is 30 percent African American. The disparity is not just along racial lines, but socioeconomic lines, too. The poor are at greater risk for developing and dying from cancer, so we are focused on how to close this gap. Our group is developing relevant questions to better understand the source of disparities and ways they could be overcome in the future. What brought you to MUSC from Johns Hopkins University? I saw that I could make a difference here in the lives of South Carolinians, and the Medical University was, and continues to be, very supportive of that goal. I saw the need and the opportunity to work with others to advance the science and to help people in real need. What keeps you motivated? We come to work each day to work on research that we hope will make a difference in people’s lives. Whether it is uncovering a new clue about the causes of cancer, developing a new strategy to prevent cancer, discovering a new way to screen for cancer, learning how to better enhance the lives of cancer survivors and their families or working to eliminate cancer disparities, we are committed to research that makes a difference.

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A TALE OF TWO SOUTH CAROLINAS Although its metropolitan areas have seen rapid growth and progress, South Carolina remains in many ways a rural state with unacceptably high rates of diabetes, stroke, cancer and heart disease. There are many reasons for this disparity, but a common denominator is clear: poor access to care and health-related information. The problem is especially pronounced in the state’s rural areas, where primary-care providers are in extremely short supply and too many families lack a thorough knowledge of healthy lifestyles. Closing the gap in cancer outcomes is the main objective of a unique research effort headed by Dr. Marvella Ford, a social epidemiologist and Associate Director of Cancer Disparities at Hollings Cancer Center who now shares space in the Clyburn Research Center. Ford and her team of investigators are leading MOVENUP, a pilot study to develop effective solutions for the underlying causes of cancer disparities. Their resources bring cancer screening and patient navigation services to underserved populations while their education programs use a “Train-the-Trainer” design to promote community health awareness, sound health habits and participation in screening.

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“In addition to helping thousands of patients directly, our study is trying to create a sustainable model for community-based health education,” Ford said. “Our outreach teams are training people to educate others in their communities about the importance of cancer prevention, screening and early detection. That lets us leverage our educational resources to provide information and cancer screening to as many people as possible.” Teran Cedric Clarke is a Train-the-Trainer participant from Columbia who sees firsthand how MOVENUP impacts the health and well-being of underserved communities. “If you know what issues and challenges exist in a community, you are better able to focus resources to address those issues and impact lives in a transformative way,” Clarke said. “The health care needs are critical in many communities, and yet access to caregivers there is so fragmented. MOVENUP has made all the difference in bridging that gap. Folks become more aware of how to manage their health, physicians become more knowledgeable about the concerns and the community is more efficiently and beneficially served,” said Clarke. “This program changes lives!” The MOVENUP project is also helping enhance the state’s research community. Working with faculty and students from Claflin University, South Carolina State University and Voorhees College, the next generation of cancer disparities researchers is learning to conduct studies to improve the prevention, early identification and treatment of cancer, particularly in high-risk populations. One student working under Ford’s tutelage is Samantha Jones, a recent graduate of South Carolina State University. “The internship changes people and helps them see the value of research,” said Jones. “After participating in the student research program, I changed my focus and I am now beginning work on my Ph.D. in pharmaceutical sciences at Florida Agricultural and Mechanical University.”

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