Thirtieth Anniversary Edition // SPRING 2015

Cancer Throughout the Years

John Kemshead, PhD Bruce Chabner, MD Chairmen, Scientific Advisory Board Scientific Advisory Board, Emeritus

The time my colleagues have spent with the Foundation was The Foundation has been in existence for 30 years and transformative. Beginning in the late 1980's, we had the belief that how have things changed during this time? On multiple the treatment of cancer would be completely changed and placed occasions you read in the news about breakthroughs in on a more rational footing by rapidly expanding knowledge of the treatment but have these really turned into a reality? genetics causing cancer. A particular meeting in the late 1980's which had the participation of many of the leading scientists and clinical researchers in the field Thirty years ago cancer treatment focused upon the was the key event. The idea was presented that the genetic changes underlying mainstays of surgery, radiation therapy and the various kinds of cancer would become the targets for new therapies, "targeted chemotherapy. In addition, diagnosis relied primarily therapies". That has proven to be true, and the concept has led to the expansion upon CT scans, X-rays and the skills of both the of the field of "precision medicine" recently endorsed by the President in his State pathologist and oncologist. Through the development of of Union speech. Many of the subsequent sessions of the Foundation dealt with the Magnetic Resonance Imaging (MRI) scanner, aspects of this larger change. There is no doubt that this concept has radically Positron Emission Tomography (PET) scans, monoclonal altered and improved cancer treatment, and given us real hope that the disease antibodies and the Polymerase Chain Reaction (PCR) can be effectively treated if we only understand its causes. technique to enable a look at gene profiles, our ability to diagnose and sub-divide tumors into different groups has markedly improved. This has led to both faster and better diagnosis, which has led to faster treatments. This Edward Frick alone has improved survival rates as, for many cancers, Chairmen of the Board, 1989-2004 early diagnosis and treatment lead to better outcomes. It has been a great privilege to be one of the founders of the However, no matter how good diagnostic tools, because William Guy Forbeck Research Foundation and then Chairman if there is not an effective treatment available all comes of the Board of Trustees for over 15 years. Our talented team to naught. Chemotherapy is the area where the biggest focused on molding the Foundation from an idea into an effective, leading-edge, advances have occurred. Thirty years ago we used worldwide organization to fight cancer, particularly pediatric cancer. Our different combinations of drugs to treat cancers and the approach was simple: bring the most brilliant scientific minds together in a small same is true today. Now, we have learned what drug group and encourage them to have a free-form discussion on a specific cancer combinations are best suited to different cancer types issue. The results were amazing, Billy Forbeck would be very pleased. With the and how to use them in higher doses. This has led to Foundation’s positive momentum and talent, the future looks extremely significant changes in the survival of patients with some promising. cancers while others remain particularly refractory to treatment. We achieved Designer drugs have been developed to block pathways IN THIS ISSUE Top-Rated Status! involved in the division of specific cancer types. With all 1 Cancer Throughout the Years of the basic research that is being undertaken to 2-3 Forum 2014: Invasion & Metastasis understand the differences between cancer cells and 4 Scientific Advisory Board Report normal cells, we are on the verge of approaching cancer Forums 2015 & 2016 treatment as a “personalized medicine”. 5 6 Scholar Retreat Today it is possible to envision that individual tumors 7 Scholar Award will be biopsied and analyzed by sophisticated 8 Tracking Charlie molecular techniques to identify what drugs are best 9 The Past & Future: From the Chairmen suited to treat the patient’s disease. This is a world 10 Benefactors away from the old style of treatment but it comes at a 11 Proof of Concept price. The world of designer therapies means a rethink in the ways drugs are developed and tested in the clinic. In addition, the costs involved in this approach to These rating sites provide treatment are not insignificant. transparency and gauges for the quality of nonprofits. 2 3

FORUM 2014: INVASION AND METASTASIS "Despite major advances in understanding the molecular and genetic basis of cancer, disease SUMMARY progression to metastasis remains the cause of >90% of cancer-related mortality. Prevailing theories hypothesize that metastases are seeded by rare tumor cells with unique properties, which may William Guy Forbeck Research Foundation XXXth Annual Forum The Forbeck Forum offered a unique function like stem cells in their ability to initiate and propagate new tumors in metastatic sites environment to discuss the latest issues in through self-renewal and differentiation." Hilton Head Island, South Carolina metastasis and new approaches that may November 6th–9th, 2014 advance our knowledge and give rise to new Zena Werb, PhD, University of California San Francissco therapies in the clinic. The discussions were wide ranging and exciting. Importantly, "Novel immunotherapeutic approaches that better harness the anti-tumor activity of cellular therapy CHAIRMEN approaches are underway. However, results from both pre-clinical and clinical trials highlight the several new collaborations arose need for a combination of both immunological approaches with those that target the Ann Chambers, PhD Zena Werb, PhD immediately as a result of these interactions. microenvironment to better treat the most aggressive forms of the neuroblastoma." University of Western University of Ontario California San • We are beginning to define new London, Ontario, Canada Julie Park, MD, Seattle Children's Hospital Francisco mechanisms that contribute to tumor San Francisco, CA invasion and metastasis. We are "Improved early detection and adjuvant therapy have facilitated progress in diagnosis and therapy recognizing that cancer is a for patients with solid tumors; however, the prognosis of cancer patients is still limited by the heterogeneous and dynamic disease that occurrence of distant metastases." can evolve in patients, and new therapies need to address this concept. Klaus Pantel, MD, PhD, University Medical Center Hamburg-Eppendorf • Progress has been made in advancing our "The translation of metastasis experiments to the clinic remains problematic. Dr. Steeg discussed the Most cancer deaths are due to metastasis – the time, and information from a primary tumor understanding of metastatic disease but fact that basically, standard phase I-III trials in the metastatic setting quantify the shrinkage of spread of cancer from its site of origin to specimen may poorly characterize individual much more is needed. We appreciate the metastatic lesions, not the prevention of their occurrence. Two types of new trial designs were distant, vital organs, and the physiological metastases that occur years later. Bioinformatic willingness of patients to participate in discussed." damage caused by tumor growth in those analyses of tumors and their metastases, over clinical trials and tissue and clinical data Patricia Steeg, PhD, National Cancer Institute organs. While the broad outlines of the process time, are providing a wealth of data to be banking as a partnership to further our of metastatic spread are known, much of the interpreted. New models are being developed to understanding and lead to improved "Understanding genes that are altered in metastasis or host genes that can regulate metastasis will details of the process remain poorly address problems in metastasis. The challenge is treatments. hopefully pave the way for identifying potential new drug targets." understood. To continue to improve cancer to learn how to harness this growing body of • There is slow progress in developing new survival rates, we must face and tackle the information to help patients with cancer. Can approaches to prevent, treat or delay Louise van der Weyden , PhD, Wellcome Trust Sanger Institute problems inherent to metastatic disease. we prevent metastasis? Can we delay metastatic disease. However, we are Cancers that are detected early, before they are appearance of metastases following primary learning that cancer can affect the whole believed to have spread to other organs, are treatment, either through information inherent body, and that the body in some cases generally treated with more success than to the primary tumor, or through life style or can limit metastatic spread. We need to cancers that are metastatic at diagnosis. anti-metastatic chemoprevention strategies? learn better how this occurs, to be able to However, even cancers that are detected early Can we learn how to better treat metastases harness this ability. will recur in some patients, but our ability to once they have developed? • There is a need for comprehensive basic predict which individuals will have recurrences research to learn more about metastasis "I wanted to extend my deepest is limited. Thus, adjuvant therapy is often given and there is a great need to identify thanks to the organizing committee to patients with early stage disease who are strategies to improve response to and all members of the Forbeck believed as a group to be risk for recurrence, targeted agents. The first of the new ideas Foundation present at the meeting. leading to over-treatment of some patients to are beginning to be translated to the clinic Their incredible hospitality and benefit a subset of them. Some recurrences can to benefit patients, but it is early days. generosity are something that made occur years or even decades after apparently a lot of difference to me...beside the successful primary treatment, and research on incredible exchange of scientific tumor dormancy is providing insights into these information we were privy to." delayed recurrences. Progress has been made in the basic biology of tumor invasion and Collaboration & Communication Nada Jabado, Ph.D metastasis, and in understanding some of the A Recent Publication Professor of Pediatrics McGill University complexities of interactions of tumor cells with The full article, Invasion & Metastasis - Montreal, Quebec, Canada host cells in their microenvironment. Great 2014 Forbeck Forum Participants Recent Advances and Future Challenges, advances have been made for many cancers, in resulted from the 2014 Forbeck Forum and terms of molecular markers/subtypes that are was published in the Journal of Molecular associated with favorable vs. poor outcome, as Medicine. well as prediction of response to a growing list The full article can also be found at of molecularly targeted agents. However, we www.wgfrf.org also recognize that tumors are not static entities, but instead evolve and change over 4 5

SCIENTIFIC ADVISORY BOARD Introducing the New FORUM 2015: Cancer Immunotherapy John T. Kemshead, PhD Collaborative Research Chairman, Scientific Advisory Board Catherine M. Bollard, MBChB, MD Grant! Washington Children’s Hospital When I decided to enroll for a The issue of funding for science and medicine has Starting in 2015, the Forbeck Foundation will PhD in the UK in the 1970's, I been made far worse with the recession but as be issuing grants to current and past Forbeck patient and they target the cells one wants to whether they are immunogenic and can the was warned by my supervisor we hopefully move back into a period of growth, Scholars who collaborate on research. eliminate. This technology has been around in therapy be repeated. Finally, there is a ques- that funding for research had will the situation improve? Funding of research projects will be based upon collaborations between two one form or another for over fifteen years, but it tion as to whether this type of therapy can be never been worse in the UK. I The Forbeck Foundation has always focused on laboratories/fellows/scholars/MDs/PhDs in now looks as if researchers have arrived at a converted into one that is available outside of should stick to medicine and funding think-tank type meetings to enhance their early years of scientific development. At Daniel Powell, PhD watershed where the therapy appears to work an academic research setting. forget about science. The collaborations between scientists with different least one of the collaborators must be either a University of Pennsylvania really efficiently for this disease. Unfortunately, reality is that the funding base The topic of immune therapy is one that fits backgrounds. In the past, I have not been past or current Forbeck Scholar. The funding there are no markers available today that avoids has shrunk in many European countries and in Some of the most exciting results in cancer perfectly with the rationale underlying the enthusiastic about diverting from this will be for two years, with the option for one the T cells attacking the patients normal as well the USA to a point where the 1970's now look medicine, in the last decade, have come about Forbeck Foundation think tank meetings. I can- programming. Faced with the dire funding additional year subject to review by the as malignant cells and this may be a significant positively advantageous for scientific research. Scientific Advisory Board. by treating relapsed patients with B cell lym- not think of a topic that is better suited to bring situation scientists are faced with today, it is time problem in the future. King’s College in London was a prestigious for change of heart. phoma with their own T cells that have been together basic reseachers in molecular biology University with a great track record for research, Preference will be given to Scholars who are modified to attack the tumor cells. T cells in the Many questions remain concerning this new and immunology with clinical colleagues to try The Foundation prides itself on trying to help but my last visit to lecture to medical students developing their own laboratories and need body form part of the cellular immune response form of personalized medicine. Will it work for and solve some of the problems eluded to in developing the careers of some of the revealed that the biochemistry staff had lost funding to enable them to establish and they normally carry out a very important other cancers, particularly solid tumors where above. Input from industry will also be encour- best scientists, both in the USA and all of their research funding and had themselves as independent investigators role in killing cells that are infected with viruses. access of the T cells to the malignant tissues is aged. If this is possible and the early clinical internationally. Through the recommendation capable of receiving major funding from essentially become a teaching facility. These cells can be modified in the laboratory more difficult to achieve? Many tumors also results prove to be substantiated then we may of our Scientific Advisory Board, the Foundation alternative sources. produce factors that inhibit T cell function so be on the brink of changing the treatment of The USA has always faired better with respect has put a program into place to support this using sophisticated molecular techniques to how does one deal with this? Apart from these specific cancers, using the bodies own cells to to the support for scientific research but even group of scientists during the early part of Grant applications will be reviewed by the change their specificity so that they can attack questions there are others regarding the resi- attack the tumor as compared to use of more here the funding base is being sliced. It is their careers. It will involve supporting Foundation’s Scientific Advisory Board as well tumor cells. Once the cells are expanded in the toxic chemotherapeutic regimens. clear that if you are both good and lucky you scientific work between at least two as outside investigators. laboratory they can be reintroduced into the dence time of the modified T cells in the body, can succeed in science but the opportunities laboratories. At least in its early years it will be are reducing. You have to really want to available exclusively to those who have been pursue a career in academic science today as Foundation Scholars and the program fits with Declaration of Interest the structure gives people little security. How the ethic of promoting collaboration between many people would want to have to raise all or different centers and scientific groups. deadline in February of part of their salaries throughout their careers to One has to be realistic that the Foundation each year. FORUM 2016: Chromosomal Instability/Aneuploidy do something that can be of significant benefit cannot cure the problem of the lack of funding to humanity? How does a career where there is for scientific research but it can play a small part Grant Application so much uncertainty about the future match in helping our scholars develop their careers and Large-scale sequencing efforts have scientists who seek to understand the with supporting a family and dealing with put them into a better position to compete for deadline in April of provided unprecedented insight into the mechanisms underlying genome instability. By everyday items such as mortgages and children. larger government grants and other types of each year. genomic changes that occur during bringing researchers together from these funding as their careers mature. tumorigenesis. We now understand that diverse fields we are hoping to develop structural and numerical chromosomal hypotheses and approaches to describe in aberrations are an almost universal feature molecular detail how genome instability of cancer and that tumors are karyotypically mechanisms shape the cancer genome and heterogeneous, constantly evolving how the condition fuels tumor evolution. ecosystems. The challenges we are faced SCIENTIFIC ADVISORY BOARD MEMBERS Angelika Amon, PhD with now is to explain what drives this The 2016 Forum on Chromosome Instability genetic plasticity and to find ways to exploit Koch Institute for Integrative Cancer Research at MIT John T. Kemshead, PhD Jan Karlseder, PhD EMERITUS and Aneuploidy will be chaired by Dr. Angelika this hallmark of cancer for therapeutic Amon of the Koch Institute for Integrative Baxter Healthcare, Chicago, IL and The Salk Institute Garrett M. Brodeur, MD intervention. The development of new Cancer Research at MIT and Dr. David Pellman University of Manchester, England La Jolla, California Webster K. Cavenee, PhD single cell analysis tools and the of the Dana Farber Cancer Institute at Harvard Nabeel Bardeesy, PhD Anthony Letai, MD, PhD Bruce A. Chabner, MD development of ever more sophisticated Medical School. The goal is to bring together Massachusetts General Hospital Dana-Farber Cancer Institute cell and animal models of genome instability Alan D’Andrea, MD The Forbeck Foundation leaders from cancer genome and chromosome Boston, Massachusetts Boston, Massachusetts have opened up new ways to tackle these Isaiah Fidler, DVM, PhD welcomes Anthony Letai, MD, instability fields to discuss the state of their Katherine K. Matthay longstanding questions. Sara A. Courtnedge, MD David E. Fisher, MD, PhD PhD to the Scientific Advisory respective fields and ways forward to translate Oregon Health Sciences Center University of California Arnold I. Freeman, MD Board. As a former Forbeck this information to the clinic. The Forbeck Foundation meeting will bring Portland, Oregon San Fransisco, California Scholar, Tony Letai has remained Ed Harlow, PhD together the leading researchers studying Michael Jensen, MD John D. Minna, MD involved with the Foundation, Michael B. Kasten, MD, PhD cancer genomes and their evolution with Seattle Children’s Research Inst. University of Texas nominated Scholars, and Philip A. Pizzo, MD Seattle, Washington Dallas, Texas collaborated on research with Jean Y. J. Wang, PhD other Forbeck Scholars. We are David Pellman, MD University of California happy to welcome him to the Dana-Farber Cancer Institute at Harvard Medical School Scientific Advisory Board. La Jolla, California 6 7

independent of DNA damage repair. For the FORBECK FOUNDATION SCHOLAR RETREAT Scholars, Cox emphasized the importance of FOCUS ON THE FUTURE: SCHOLAR AWARDEES cultivating and training the next generation of “systems” level. Bob S. Carter, M.D., Ph.D., an scientific investigators. Louise van der Weyden, PhD Lake Geneva, Wisconsin invited mentor and Chairman of Neurosurgery at Rosandra Kaplan, MD Scholar Award National Institute of Health Wellcome Trust Sanger Institute September 11th–14th, 2014 the University of California, San Diego, shared an The final session of the meeting focused on Dr. Van Der Weyden is Forbeck Scholar Award recipients are extraordinary career that spans the discovery of Resistance Mechanisms. Mari-Francis Arteaga, Dr. Kaplan received her invited to participate in the Foundation’s a Senior Staff Scientist Clark Chen MD, PhD clinical importance of Ras in prostate cancer, the Ph.D. (Universitatsklinikum Munster, Germany) MD from Dartmouth Scholar Retreats for the subsequent four at Wellcome Trust University of California construction of chimeric T-cells as a tool for described the importance of PHF8, a lysine Medical School and years. This gives them further Sanger Institute (WTSI) San Diego, CA molecularly targeting oncogenes, and the demethylase, as a molecular sensor for completed her pediatric opportunities to interact with their peers residency training at in Cambridge, UK. She and meet with different groups of discovery of exosomes as a clinical diagnostic mediating retinoic acid treatment response in Harvard Children's received her PhD in international cancer experts. Existing and therapeutic platform. For career guidance, acute promyelocytic leukemia (APL). Cory Hospital Boston, and cancer biology from awardees have found these experiences The meeting began with a talk by the keynote Carter emphasized the importance of Johannessen, Ph.D. (Dana Farber Cancer speaker, David Cheresh, Ph.D., Vice Chairman of invaluable in developing collaborations as collaborative endeavors and innovation through Institute) reviewed his work demonstrating Boston Medical Center. Dr. Kaplan further University of Sydney, Australia, before moving well as opening up a variety of career Pathology, University of California, San Diego inter-disciplinary investigations. molecular pathways responsible for acquired pursued a fellowship in Pediatric to the UK to work as a Post-Doctoral Fellow at opportunities. Joining this group also that described his fascinating journey from Hematology and Oncology at Memorial Sloan- WTSI. In Professor Allan Bradley's laboratory, The session on Friday afternoon focused on therapeutic resistance to molecularly targeted offers awardees the opportunity to apply studies of antibodies to the discovery that Kettering Cancer Center and Weill Cornell her research is focused on generating and for other programs sponsored by the Epigenetics. Grant Challen, Ph.D. (Washington agents. Kristopher Sarosiek, Ph.D. (Dana Farber defined the role of integrin in angiogenesis, Medical Center, where she was Chief Fellow. characterising mouse models of cancer. This Foundation that are only open to Forbeck University School of Medicine) spoke on the Cancer Institute), discussed assessment of including a detour through a landmark Supreme apoptotic potential in various organs to better She did her postdoctoral research work in the was further built on in Dr. David Adam's Scholars. During this four-year period, the importance of DNA methyltransferases and DNA Foundation will pay all expenses to attend Court case. In the early 1990’s, David had made understand developmental programming. I laboratory of Dr. David Lyden. Dr. Kaplan was laboratory where she used insertional methylation in hematopoietic stem cell fate the meetings and an honorarium to the seminal discovery that angiogenesis could spoke in this last session describing miRNA appointed Assistant Professor at Weill Cornell mutagenesis (retroviruses and transposons) to decision. Gary Chung Hun, Ph.D. (University of individuals at the end of their tenure be inhibited by blocking surface receptor on Medical College and Assistant Member at identify genes that co-operate in California San Diego) described his work degradation as a novel mechanism of acquired periods. endothelial cells. He tested RGD peptides Memorial Sloan Kettering Cancer Center in tumorigenesis. Most recently, she has elucidating the molecular physiology associated resistance to chemotherapy. The degradation of supplied by Merck for their anti-angiogenic 2006. In 2010 she joined the Pediatric Oncology undertaken a research program that focuses on with aberrant Epidermal Growth Factor Receptor key miRNAs results in simultaneous de- effects in tumor models. Integra, a company Branch of NCI. She is a clinician and physician understanding the nature of metastasis, in (EGFR) signaling. Chris Vakoc, Ph.D. (Cold Spring repression of multiple DNA repair process. Important Scholar that co-owned five patients (with the Burnham scientist with active translational and clinical particular melanoma metastasis. Harbor Laboratory) discussed the role of the BET Moreover, such resistance can be circumvented Institute) to variants of RGD peptides, sued research interests focused on the mechanism of Dates bromodomain protein BRD4, as a drug target in by retroviral gene therapy. Merck for infringement of patent rights. The cancer spread. Scholar Award acute myeloid leukemia. Anindya Dutta, M.D., Mario Shields, PhD suit was ultimately reviewed by the Supreme Cold Spring Harbor Laboratory Applications due April 15, 2016 Ph.D., an invited mentor and Chairman of Court. The Court decided in favor of Merck/ The breadth and the depth of the scientific Chad Pecot, MD Biochemistry and Molecular Genetics, University Cheresh and held that “the use of patented discussion at this retreat are both University of North Carolina Dr. Shields is a Collaborative Research Grant of Virginia, shared with the Scholars an Appliations due April 15, 2016 compunds in preclinical studies is protected... as impressive and extraordinary. The unique Chad Pecot is an postdoctoral fellow in intellectual odyssey through molecular presentation format provided a forum for long as there is a reasonable basis for believing Assistant Professor at the laboratory of Dr. Upcoming Retreats mechanisms that govern DNA replication and the consequential dissection of the central that the experiment will produce ‘the type of the University of North Mikala Egeblad at Cold October 1-4, 2015 non-coding RNAs critical for regulating these questions of the various fields, affording information that are relevant to an IND and Spring Harbor October 8-11, 2016 cross-fertilization of ideas and concepts as Carolina who NDA.'” Cheresh gave a mesmerizing first person mechanisms. Dutta’s advice to young Laboratory. He is October 12-15, 2017 invitees build on and critique the ideas of specializes in lung investigators is that “it is always worthwhile to October 11-14, 2018 account of the scientific and personal context of each other. The small group size facilitated cancer. His laboratory employing a novel take the ‘high road’ when you are placed in an October 10-13, 2019 this important Supreme Court case that meaningful intellectual discourse, exchange is located in the approach of live animal imaging to dynamically continues to shape investigational use of unfortunate situation. The individuals that you of friendship, and guided mentorship. Lineberger Cancer Center and is focused on monitor interactions between cancer cells and patented reagents in research. As a life lesson, lash out against today will inevitably become Excitement of discovery and advancing the studying metastatic biology cancer. Because components of the tumor microenvironment. Focus Meetings he emphasized the need to doggedly pursue your Reviewers in the near future.” frontier of knowledge was palpable with metastases are responsible for the death of More specifically, he is investigating how those studies that are of personal importance, every exchange. Without a doubt, the The Saturday morning session focused on Tumor nearly all lung cancer patients, the ability to changes in the extracellular matrix molecules Focus meetings give Scholar Awardees irrespective of the obstacles. ideas and talents cultivated by this Retreat the opportunity to host their own think Metabolism. Julie-Aurore Losman, M.D., Ph.D. inhibit this process is vital. Using nanoparticle- surrounding pancreatic cancer cells regulate will play key roles toward scientific tank with a topic and participants of their The scientific session on Friday morning (Dana Farber Cancer Institute) showed work based platforms, he is interested in using RNA- growth, metastasis and resistance to therapy. advances that ultimately benefit humanity. choosing. These meetings are a vehicle to focused on Cancer Genomics. Dereck Chiang, suggesting that the EGLN1 complex, a critical interference approaches to develop novel He received his PhD in Life Sciences from Northwestern University. further the research and professional Ph.D. (Novartis) discussed the challenges that oxygen sensor for cellular metabolism, may therapies for this problem. As a prior cancer development of Forbeck Scholars. he faces daily in terms of the clinical translation harbor functions outside of its canonical role. patient, his passion is to make high-impact Scholars have used these meetings as a of the ever-expanding cancer genomic Kathryn Wellen, Ph.D. (University of discoveries in cancer biology and translate these way to delve deeper into a topic they landscape and the need for thoughtful clinical Pennsylvania) provided data suggesting that to the clinic as rapidly as possible. want to learn more about or to develop a trial design. Sharon Diskin, Ph.D. metabolic disturbances can translate into Sponsored by: Fran Zappitelli paper. The Foundation will assist with (Children’s Hospital of Philadelphia) unveiled genomic instability and altered DNA damage logisitics, but otherwise it is the Scholar's novel single nucleotide polymorphism that may repair. Michael Cox, Ph.D., an invited mentor meeting. underlie unique clinical features of and a tenured Professor at the University of Sponsor A Scholar Applications for a Focus meeting can be Wisconsin, described his pioneering work neuroblastoma subtypes. Chris Putnam, 4 year pledge, $1,000/year submitted any time. Details can be found Ph.D. (University of California, San Diego) uncovering mutations that mediate evolution of on the Foundation website, provided an overview of how model extreme resistance to ionizing radiation and the For more information please contact "Thank you to our mentors who provide www.wgfrf.org. pertinence of these mutations to therapeutic [email protected] organisms, such as the baker’s yeast impressive presentations and provide great Saccharomyces cerevisiae, can be used to development for cancer patients. Importantly, wisdom to carry our Scholars throughout their dissect complex genetic interactions on a many of these mutations modulate processes careers." - The Forbeck Foundation 8 9

FROM THE CHAIRMAN’S DESK Tracking Charlie A Note From the Past Cancer won't stop him from his 400 mile journey... The Forbeck Foundation has been a Chairman, was a legacy member of the to the next humanitarian medical My name is Charlie Howden and I have had a dream of paddling the west coast of success because of the community Board. His father, Sam Irmen, was a need. Thirty years is proof that support from South Carolina, Lake founding member of the Foundation, mankind can address and conquer Costa Rica to raise money for a charity. Who knew that I would be doing it while Geneva, the Chicago Board of Trade co-worker and dear friend of the what nature has created. Your battling Pancreatic Cancer. and the scientific community. The Forbeck family and gave Billy's eulogy. support means the Foundation's Chicago community, in large part, The list of founders who gave the initial efforts will always be able to move I am from Eastbourne, East Sussex in the South East of England and have always provided the seed money to get these funding for these meetings were co- forward to the eventual cure, no been keen in all sports particularly those that involved the water. In 2010, I was efforts off the ground. Our highly workers and family friends of the matter what the medical introduced to paddle while working on yachts in South Florida. From the first time reputable Scientific Advisory Board Forbecks. To this day, the Board, along challenges are. on the water I fell in love with the sport. I knew that someday I would plan an members give their personal and with new members continues to be expedition style endurance paddle as it suited my determined nature and my love professional experience to make the made up of friends of Billy Guy, children of exploring. Foundation a great success as well. of founding board members, family and friends. I am very proud to be a part of There are almost too many these efforts and to be involved in the One day I put a route into the navigation system along the Pacific Coast of Costa supporters to thank. The balance of transistion of the Foundation. Rica from its northern border to its Southern. It took about 20 minutes to decide professional and personal lives, along with combined financial this was going to be the route I would attempt. Then I decided that I wanted to do We all began with the hope that we committments, go into making this this to raise money for a charity. A friend suggested the William Guy Forbeck would live long enough to see the initiative work. Bill Terlato has Research Foundation (WGFRF), a cancer research organization. It immediately benefits of our efforts. The medical received Emeritus Status for his made sense as I have lost friends to this terrible disease. community has demonstrated that we service on the Board. Ed Frick served have come a long way. My hope for the as Chairman of the Board for years. Things were falling into place and I was aiming for March of 2013. But then…. the next generation is that they "see the He was George Forbeck's college Charles H. Jesser, CPA cure" and can move the Foundation on results were positive. I was diagnosed with Stage IV pancreatic cancer at the roommate. Terry Irmen, also a past President, Board of Directors beginning of August 2013. This was a strange coincidence after having just decided to raise money for cancer research. THE NEXT 30 YEARS In September 2013 I started my chemotherapy and my road to recovery. During this time, paddling kept me dreaming, pushing myself, and my mind positive. It It is hard to believe that 30 years We will create more programs to has kept me strong, and my dream alive to raise money for cancer research. After have passed since Billy died, that a expedite and fund research. I expect a year of chemotherapy and a course of radiation my recent scans have come back neuroblastoma-based foundation has to see the INRG database become a negative. There is still a long road ahead but throughout this time I have learned I lasted 30 years, that so many of our tool used around the world for need to live my life. There is no point wasting time wondering what this disease trustees and supporters have been researchers and physicians, just like the could do to me. with us for 30 years, or that staging system created at the first neuroblastoma is still one of the Forum. I expect our amazing Scholars By no means am I back to 100% of my normal self but this was meant to be a deadliest of childhood cancers. It is to do great things and come up with challenge. So I have decided to proceed with the paddle. It’s time to finish hard to imagine what the next 30 brilliant research, especially with the planning and get started on the 450 mile challenge. years will bring, but I do have an idea opportunity of the new Collaborative of some things that I expect to Research Grant. I hope the The support I have had from friends and family has given me hope that I can live happen. Neuroblastoma Consortium, which we helped create, builds strength in Jamie Forbeck Collins my life and beat this disease. This paddle will raise money for cancer research. The Foundation will continue to grow numbers as NB foundations around the Foundation Secretary and Board Member More importantly I want to give hope to all those battling cancer or to those who and do more in the fight against world work together to fund have friends or family battling this, that it is not an end, but a journey of something cancer. Our mission is to shorten the international tools and make help new. time table of cancer research, and available to everyone. although progress has been made in Sincerely, 30 years, we have more to do! I hope that the Foundation won’t be Note: Charlie plans to make his journey needed long before the end of the next Charlie in May 2015. 30 years. 10 11

BENEFACTORS Mr. George B. Farnsworth Joel & Michele Kennedy Rancho Santa Fe Foundation MAKE A DONATION Mrs. Jennifer Forbeck Teresa & Reggie Kerr Mrs. Frederick L. Reed Alben F and Clara G Bates Foundation Mr. & Mrs. F J Frazier III Caroline Kinzer Mr. & Mrs. Leonard Reich It is through your generous support that continuing research in the field of childhood cancer can be ensured. Contributions are tax deductible for Mr. & Mrs. Steve Bailey Mr. & Mrs. Edward R. Frick Mr. William M. Kinzer Mr. & Mrs. William P. Reilly federal IRS purposes. The IRS file number is 580063499. To make a donation please visit wgfrf.org or choose WGFRF as your charity of choice on Deedee Baka Mr. & Mrs. William B. Gage Jr. Ms. Mary anne Kirchschlager Drs. Anthony Ricci Smile.Amazon.com. Mr. & Mrs. Matthew Garrison Andrew Kubicsko Mrs. Mary Kay Ring Thomas Bence Visit www.wgfrf.org Mr. & Mrs. Frank D. Gazzolo Mr. & Mrs. Michael P. Kyle Mr. & Mrs. Kurt Ripkey Mr. & Mrs. Vincent Benedetto Contact [email protected] Big Foot Lions Club Mr. & Mrs. Robert M. Geldermann Mr. & Mrs. Montague T. Laffitte Mr. & Mrs. Ronald Sarna Mail to the Address William Guy Forbeck Research Foundation Jan Bjorkman Mr. & Mrs. Stephen R. Geldermann Mark Lahey Barton Schlageter 23 Peninsula Drive, Hilton Head Island, South Carolina 29926 Mrs. Ralph Bogan Mr. & Mrs. Thomas A. Geldermann Lake Geneva Country Club Linda & Ken Schmidt Shop at Smile.Amazon.com Mr. & Mrs. John A. Bollero Jr. Geneva Advisors, LLC Mrs. Tobey Lannert Mrs. John M. Smyth Ann E. Brandt Mr. Matthew M. Gerdes Mr. & Mrs. G. Curtis Lansbery Mrs. Robert W. Smyth Margaret Cardiff Mr. Eric Geschke Mr. Hayden Leason Vince & Nona Sorren Mr. & Mrs. Thomas J. Cashman Mary Lou Gibson Mr. & Mrs. Michael H. Leason Ms. Holly Starck Smile.Amazon.com donates 0.05% of each purchase to the charity of your choice. Just login to Smile.Amazon.com with Susan Casscells Gordy's Lakefront Marine Ms. Ann M. Lehman Mr. & Mrs. Tobias Steivang the same login information for Amazon.com and select the William Guy Forbeck Research Foundation as your charity of Mrs. An Grosshuesch Mr. & Mrs. William Lehman Dr. & Mrs. Robert A. Cohen Mary Stinebrink choice! Each time you make a purchase, a small portion will go directly to the Foundation to support our programs. Mr. & Mrs. David B. Collins Mrs. William Grunow Mr. & Mrs. Craig Lindmark Ms. Jane P. Sweetsir James Connors Mr. & Mrs. Don M. Guscio Mrs. Sandra Loebmann Tallman Equiptment Company, Inc. Mr. & Mrs. Michael J. Corey Mr. & Mrs. Charles H. Harker Mrs. James Maddock Mr. & Mrs. Luis E. Taveras, PhD Mr. & Mrs. Joseph Cramblit Mr. & Mrs. Hagen Harker Ms. Cindy Maher Terlato Family Foundation Mr. & Mrs. Edward A. Culbertson Gary & Sharon Harrison Mr. & Mrs. Michael A. Mason Mr. William A. Terlato Mr. & Mrs. Arvid Dahlstrom Mr. & Mrs. John Hatch McKee Family Foundation The Boeing Company Mr. & Mrs. Don Hedberg "The most beneficial parts of the Scholar Retreat were the networking Andrew Dammeir Mr. & Mrs. Harris McMurry The Charles Schwab Corp Foundation PROOF OF CONCEPT Daniels Sentry Foods Mr. & Mrs. Paul Hoffman McNabola Law Group, PC Mr. Thomas Theys opportunities and the ability to get really good feedback on my research." Mrs. Judith A. Howe Richard Meister Mr. & Mrs. Frank Todd Mr. & Mrs. Terry Daniels Kristoher A. Sarosiek, PhD Mr. & Mrs. Hanley Dawson Mr. & Mrs. Daniel R. Huber Mr. & Mrs. Robert B. Moore Stephen & Susan Tolbert Dean & Lois Griffith Foundation Mr. & Mrs. Paul Hull Morgan Stanley Mr. & Mrs. William Turner The Forbeck Foundation strives to achieve drug resistant cells, and patients with this Kristipher A. Sarosiek, PhD Mr. & Mrs. Chandler Dimberg Mr. Jay P. Ieronimo Ms. Avis R. Murray Mr. & Mrs. Nicholas Tzitzon collaborations between clinicians and research- disease frequently show evidence of Dana-Farber Cancer Mr. & Mrs. Richard F. Dousman Mr. & Mrs. Jim Ieronimo Mr. & Mrs. Jeff P. Noll Ms. Molly Vaile ers to advance cancer research. Forbeck oncogenic Ras activation. Finally, by studying Institute J.P. Morgan Chase Foundation Irene Oblen Boston, MA Catherine Dowd Ms. Lael Vandenburgh Scholars Kristopher A. Sarosiek, PhD and Kris the mechanism by which Ras effector signaling Mrs. Doris Elaine Jacobsen Mr. John O'Neill Lee Dowsett Mr. & Mrs. Francis E. Wall Cameron Wood, PhD recently published a drives resistance, we identified a downstream Mr. & Mrs. Charles H. Jesser Mr. & Mrs. Roger L. O'Neill Arnold & Nancy Warner Mr. & Mrs. Charles H. Drawdy Sr. paper in Science Magazine, December 2014 protein, BCL-XL, whose pharmacological Mr. & Mrs. Charles Ebeling Ms. Pede Jesser Otzen Family Foundation Ms. Christine Weirath issue, titled RAS signaling promotes resistance inhibition may be an effective therapeutic Mr. & Mrs. Galen Eckland Jesser, Ravid, Jason, Basso and Palmetto State Bank William Blair & Company to JAK inhibitors by suppressing BAD-mediated strategy in this disease. Mr. Peter H. Edwards Farber, LLP Barbara Phillips Ms. Jeannette M. Windon Kris Cameron Wood, PhD apoptosis. Sarosiek and Wood met as Forbeck Mr. & Mrs. William J. Johnson Mrs. Walter R. Phillips Mr. & Mrs. William W. Wolf Duke University James Ehlen It is hard to quantify the accomplishments of Mrs. Margaret Eklof Mr. & Mrs. Gary M. Jouris Mr. & Mrs. Anthony Picone Mr. & Mrs. David L. Wright Scholars. Durham, NC the Forbeck Foundation. Collaborations and Mrs. Linda P. Ellis Mr. & Mrs. William O. Kasten Posen Family Foundation Francis J. Zappitelli The study examines the phenomenon of papers like this frequently result from Forbeck Susan Evans Ms. Irene Keeley Ms. Sally Prio resistance to JAK2 inhibitors, a family of drugs used in the treatment of JAK2 mutation meetings but we don’t always hear about MEMORIAL BLUE JEAN BALL SPONSORS BOARD OF DIRECTORS positive myeloproliferative neoplasms. They them. Thank you to Dr. Sarosiek and Dr. Wood found that the activation of pathways for sharing this paper and for collaborating to downstream of the oncogene Ras can drive expedite cancer research. Charles Boehland Jean Myers Allis Blue Denim Donors President EMERITUS resistance to these drugs, that inhibition of Lindsay Buchanan Dennis P. Lannert Energy.me Charles H. Jesser, CPA David R. Barry, Jr. these key RAS effector pathways can sensitize Frank Galluci Jr. Thomas Patrick O'Neill Gordy's Lakefront Marine Richard Ring Vice President Joseph W. Black, MD Cynthia Gatziolis Roger & Darlene O'Neill Will Sander David Collins Anthony George Forbeck Hon. Sol Blatt, Jr. Carla Smyth Research Sponsors Secretary Kevin P. Forbeck James A. Buchanan Harry Strouse Eklof Jr. Anthony & Tina Ricci IN APPRECIATION From the beginning, Billy's family has been very businesses and foundations, whose financial William G. Forbeck Jamie Forbeck Collins Charles H. Drawdy Gerald Tuite Michael & Cathleen Corey all the people who have worked to support assures the continued work in Cancer Jane M. Frackelton Treasurer Edward R. Frick greatful for Helen Wageman research. William H. Frackelton Retreat Sponsors Matthew M. Gerdes make the activities of the Foundation a success. Thomas Ward Jennifer K. Forbeck Pearl Geshke William Blair & Company Benjamin A. Collins They are greatful to the Scientific Advisory Marshall Wright Thomas A. Geldermann Sincere Thanks, Mentor Sponsors Phil Gregorich Chandler Dimberg Ernest F. Hollings Board and the Forum participants, the scientists Peter Kinnick Geneva Investment Advisors, LLC HONORARIUM William Herbkersman Terence J. Irmen and clinicians whose leadership and effort are The Forbeck Family Richard A. Kinzer Dalco Metals, Inc. the front line in the war against Cancer. Special Kinzer Benjamin Collins Aaron H. Jesser T. L. Sam Irmen Helen Leason Special thanks to... appreciation goes to the Foundation Directors, Grant Challen William O. Kasten Ann Huber Kasten Robert Murray Sr. Terlato Wines International the Scientific Advisory Board and volunteers Michael H. Leason Montague T. Laffitte E Street Denim whose thoughtfulness, time and energy have Harris McMurry Hayden Leason Chinawest Jewlers done so much for the success of the Foundation Luis E. Taveras, PhD Joseph Laver, MD Maureen Wheeler William A. Terlato and the Forums. Most importantly, many thanks go to the hundreds of donors, individuals 23 Peninsula Drive Hilton Head Island, South Carolina 29926

Save the Dates

GOLF OUTING FRIDAY, JUNE 19th, 2015 11:00 am Shotgun Start Lakewood Golf Club Lake Geneva, Wisconsin Register under About Us/Golf Outing at wgfrf.org

BLUE JEAN BALL SATURDAY, OCTOBER 3rd, 2015 6:00–10:00 pm Lake Geneva Country Club Lake Geneva, Wisconsin Purchase tickets under About Us/Blue Jean Ball at wgfrf.org