2013 REPORT ON GIVING FOR THE

Michael CuccioneFoundation

Michael CuccioneChildhood Cancer Research Program

MAKING A DIFFERENCEThrough your support, research into childhood cancer has the potential to improve the lives of millions of people affected by the disease worldwide. In keeping with Michael Cuccione’s belief that the cure will be found within a child, researchers in the Michael Cuccione Childhood Cancer Research Program (MCCCRP) are working to find the causes of cancer, to develop enhanced treatments and, ultimately, to find a cure.

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I commend the Michael Cuccione Foundation for your vision, patience, and steadfast commitment to childhood cancer research. As you and the scientific community know, the search for effective cancer treatment alternatives is a lengthy and intensive process. Your dedicated, long-term funding support is invaluable.

By nurturing and supporting trainees through the Michael Cuccione Fellowship Endowment for Oncology Research, you are giving masters, doctorate and postdoctoral candidates the opportunity to receive extensive training at our facility. These trainees will bear the standard for innovative discoveries and, with your support, will become tomor-row’s leaders in childhood cancer research.

The brain tumour-specific competitive award being offered by the Michael Cuccione Foundation is another new and innovative initia-tive that will not only provide financial support to a number of brain tumour research projects but will also be influential when our new research team members apply for future funding.

I’m pleased to let you know that the Michael Cuccione Foundation’s support for the Childhood Cancer & Blood Research BioBank was extremely successful. Its creation has not only served the needs of scientists in childhood cancer research, it has also proven the profound need for an institutional BioBank for use by researchers in all other areas of child health as well. Your support toward the cancer-specific BioBank has leveraged an additional donation to create a BioBank to serve the entire Child & Family Research Institute. The BioBank, in addition to being a valuable scientific resource, is helping to reinforce our international reputation as one of the world’s leading centres of excellence.

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We are honoured to have the support of the Michael Cuccione Foundation. Thank you for inspiring and supporting our researchers in their search to find alternative and effective treatments for childhood cancer and blood diseases. I’m proud to share with you an overview of the successes that have been accomplished as a direct result of your leadership and generosity.

Dr. Kirk Schultz, Director Michael Cuccione Childhood Cancer Research Program and Childhood Cancer and Blood Research at the Child & Family Research Institute at BC Children’s Hospital

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Casey Wright, age 12

Childhood Cancer and Blood Research

The MichaelCuccione ChildhoodCancer Research Program

Blood DisordersProgram

Clinical ResearchUnit Program

Tumour and Transplant Immunology Program

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In BC, about 130 children under age 15 are diagnosed with cancer every year. All of them are seen at BC Children’s Hospital. As you know, children and adolescents with cancer are not simply little adults with cancer. Children’s cancers differ greatly from adult cancers in the way they look and grow, and how they respond to treatment. The chance for complications in the treatment of cancer in kids can be high and the toxic side effects caused by the medications used to save them can have a devastating and long-lasting impact on a child’s health.

The MCCCRP is one of four key programs within the Childhood Cancer & Blood Research cluster at the Child & Family Research Institute (CFRI). Our researchers share the Michael Cuccione Foundation’s vision of a world that is free of cancer for children and families. Conducting ground-breaking research that leads to the prevention of toxic side effects of anti-cancer drugs, the discovery of new life-saving treatments and cures for childhood cancers is at the heart of everything we do. With your generosity, our world-class team of investigators is bringing hope to children and families living with cancer in BC, across Canada and around the world. Thank you for your support and leadership in maintaining this important area of research.

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Jayden Pun, age 11

CHILDHOOD CANCER IN CANADAToday, more children survive cancer than ever before – the cure rate is more than double that from the 1950s. Still, about 1,000 children under the age of 18 develop cancer each year in Canada. Despite new treatments, it remains the most common disease-related cause of death in children one to 19 years of age. Children who do survive often suffer disabling side effects, such as deafness or heart failure, caused by the very drugs that saved their lives. With your support, our investigators are researching new treatments to help children not only survive cancer, but also to prevent the toxic side effects caused by anti-cancer drugs.

The impact of cancer treatments on children’s growing bodies can range from mild to severe. Cancer treatments – radiation, chemotherapy or stem cell transplants – involve killing cells that grow quickly, such as cancer cells. In a child, many healthy cells throughout the body are growing fast, too. These treatments can damage normal growing cells and keep them from developing the way they should.

Despite the risk of complications, childhood cancers respond well to today’s therapies. Thanks to child-specific cancer research and improved treatments over the last 30 years, children with cancer have a better chance of living a longer life than ever before. In fact, if diagnosed and treated correctly, the overall cure rate for children with some types of cancer are as high as 80 per cent. Cure rates will continue to rise with the medical advancements made possible through your support of childhood cancer care and research.

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14%Bone and soft tissue sarcomas

12%Neuroblastoma

5%Renal tumours

2%Hepatic tumours

2%Germ cells

1%Other non-specified

1%Other malignant epithelial

33%Leukemia and lymphoma

30%Brain tumours

Mortality rates in Canadian children up to 14 years of age from 2000–2007

According to Canadian Cancer Statistics, leukemia and lymphoma are the most commonly occurring type of cancers in Canadian children, followed by brain cancer, and bone and soft tissue cancers.

The top four types account for 89 per cent.

33%

30%

14%

12%

5%

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BUILDING A WORLD-CLASS RESEARCH TEAM The top-notch research team you are funding through the MCCCRP was hand-picked by Dr. Kirk Schultz, director of both the MCCCRP and the Childhood Cancer and Blood Research cluster. This outstanding group of researchers is united by one purpose: to save children’s lives and to improve their health and quality of life. Through your support of their work, the MCCCRP is helping to make sure research translates into better, less invasive treatments – treatments that do less harm to growing children and teens.

our researchers at a glance

Dr. Kirk Schultz, Director

research focus: leukemias

Dr. Schultz’s research centres around the immune system, childhood leukemia, blood and marrow transplantation, and tumour immunol-ogy. His research looks at ways to harness the immune system to cure childhood leukemia and to use blood-derived stem cells to cure other life-threatening childhood diseases.

Read more about Dr. Schultz and his research team on page 19.

top row: Dr. Kirk Schultz, Dr. Catherine Pallen, Dr. Sandra Dunn

middle row: Dr. Poul Sorensen, Dr. Chinten James Lim, Dr. Gregor Reid

bottom row: Dr. Christopher Maxwell, Dr. Rod Rassekh, Dr. Rebecca Deyell

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Dr. Catherine Pallen, Associate Director

research focus: metastasis

Dr. Pallen and her team are investigating how the actions of a group of key regulatory molecules called protein tyrosine phosphatases are altered in various types of pediatric tumour cells to promote malignant cancer cell behaviours. In other words, with the goal of identifying new anti- cancer therapies, her research looks at new ways to prevent a particular type of cancer from growing and spreading.

Find out more about Dr. Pallen’s research on page 18.

Dr. Sandra Dunn, Scientist

research focus: brain tumours

Dr. Dunn’s team is working on identifying new molecular targets for the treatment of cancer. Coupled with these activities she is also developing molecular tests that will select patients who are at very high risk of relapse and then match their profiles to novel drug candidates. This work is being conducted in collaboration with the neurology, neurosurgery and neuropathology teams at BC Children’s Hospital.

Read more about Dr. Dunn’s recent work on page 17.

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Dr. Poul Sorensen, Senior Scientist

research focus: solid tumours

Dr. Sorensen’s research group is investigating how genomic alterations disrupt signal transduction in pediatric malignant tumours, and how genome-wide changes in gene expression relate to signalling alterations in these tumours. The group is particularly focusing on how such alter-ations influence metastatic disease in pediatric cancer, and how genetic alterations affect cell stress signaling pathways. The ultimate goal is to identify new therapeutic targets in childhood cancer.

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Dr. Chinten James Lim, Scientist

research focus: cancer cell chemoresistance

Dr. Chinten James Lim’s research is directed to understanding how cell adhesion molecules contribute to chemotherapeutic relapse in pediatric leukemia, specifically, in T-acute lymphoblastic leukemia (T-ALL). Having demonstrated this in an in-vitro model for T-ALL, Dr. Lim and his team are now expanding the study to include T-ALL lymphoblasts derived from patient samples obtained at BC Children’s Hospital through the BioBank. Dr. Lim collaborates with fellow MCCCRP researchers Drs. Reid, Pallen, Schultz and Maxwell.

Dr. Gregor Reid, Scientist

research focus: immune therapy for leukemia

The focus of Dr. Reid’s research is the development of new immune-based therapies for childhood cancer, with a focus on leukemia. He and his team use a combined approach that involves patient samples and animal models of disease to identify the best ways to trigger the immune system to attack cancer cells.

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Dr. Christopher Maxwell, Scientist

research focus: cancer cell division

Dr. Maxwell’s research group is working toward the development of safer, more effective medicines for children and young adults with cancer. Dr. Maxwell studies the organization of cancer cells’ internal roadways with the goal of identifying new targets that will block cancer cell growth. Dr. Maxwell works closely with Dr. Dunn in the study of pediatric brain tumours and hereditary breast cancers that affect young women. He is also working with Dr. Lim in the study of ways in which cancer cells grow and divide, and with Dr. Reid in the study of hereditary tumours that wrap around nerves in the body.

Dr. Rod Rassekh, Clinician-Investigator

research focus: pharmacogenomics of adverse drug events

Dr. Rassekh is part of a national research team that is identifying the genes responsible for toxicity from chemotherapy. A genetic test has been created that will be offered clinically to children diagnosed with cancer in BC starting this year. It will help identify which children are at risk of heart damage or hearing loss from chemotherapy, potentially allowing doctors to adjust their treatments to reduce the risk. Dr. Rassekh is also working on a trial that aims to protect young children with cancer from suffering hearing loss caused by chemotherapy.

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Shaelyn Stonnell, age 8

feature researcher

Dr. Rebecca Deyell, Clinical Investigator

research focus: neuroblastoma

The newest recruit to the MCCCRP is Dr. Rebecca Deyell, a clinical investigator at the CFRI and an oncologist at BC Children’s Hospital. Her areas of research include neuroblastoma, the late effects in survivors of childhood cancer, clinical trials in pediatric oncology and developmental therapeutics.

“My disease-specific focus is neuroblastoma, and specifically, older children and teens with neuroblastoma, the most common extra-cranial solid tumour of childhood. As part of the Michael Cuccione Childhood Cancer Research Program, I am proud to be working toward finding the best treatments for children and adolescents with cancer. ”

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Dr. Deyell completed her pediatric residency at Alberta Children’s Hospital in Calgary and a fellowship in Hematology/Oncology/Blood and Marrow Transplant at BC Children’s Hospital. She has a Masters in Health Science from the University of British Columbia as part of the Clinician Investiga-tor Program. She also completed additional clinical and research training in neuroblastoma and developmental therapeutics at the Children’s Hospital of Philadelphia in 2010-11. Dr. Deyell recently returned to BC Children’s to join the Division of Hematology/Oncology/Blood and Marrow Trans-plant and is combining her clinical work with clinical research in pediatric oncology.

One of Dr. Deyell’s main research areas focuses on neuroblastoma in older children and youth. Neuroblastoma accounts for 10 per cent of pediatric cancer mortality. Its incidence peaks in infancy, with an average age of 17 months at diagnosis. Neuroblastoma is usually rare in older children and adolescents, and those who do have it typically have a slow-growing disease. In a study, Dr. Deyell is using data from the International Neuro-blastoma Risk Group on 8,800 children with neuroblastoma to determine how age affects this group, and to define the clinical and biological predic-tors of overall and cancer-free survival. She is also involved in determining whether currently accepted treatments for high-risk neuroblastoma are effective for these patients.

Dr. Deyell also studies the late effects of cancer and its treatment in survivors of childhood, adolescent and young adult cancer. She is currently involved in a project that will determine if survivors are at increased risk of using prescription mental health drugs, compared to their peers. She is also interested in developing early phase clinical trials in pediatric oncology to help facilitate the rapid transition of new targeted drug therapies from the lab to the patient.

Read more about Dr. Deyell’s collaboration with Dr. Schultz on page 19.

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SUCCESSES IN RESEARCH

In the past year, the MCCCRP team has achieved significant success. The following stories illustrate some of the innovative research that is enabled by your contribu-tions to the MCCCRP.

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Sierra Whyte, age 5

Shrinking Brain Tumours and Preventing Their ReturnMCCCRP and other CFRI researchers have discovered that stopping the action of a single protein can potentially shrink brain tumours and prevent their recurrence without harming surrounding brain cells. Annually, more than 3,300 children in North America are diagnosed with brain tumours, including 30 British Columbian children. A third of these children will die from the disease.

One possible key to reducing this toll is PLK1, a protein required by cells to divide. PLK1 is far more abundant in cancer cells – which undergo rapid, unregulated growth – than in healthy cells. Dr. Sandra Dunn’s CFRI research group has shown that when PLK1’s action is inhibited in brain cancer cells grown in the lab, the cells not only stop dividing, they die.

In addition, the researchers demonstrated that inhibiting PLK1 also stops the growth of cells that are the seeds of brain tumours, called brain tumour initiating cells (BTICs). The researchers isolated BTICs from 14 brain tumours removed from children at BC Children’s Hospital. Lab studies revealed that when the researchers suppressed PLK1’s action, those tumour cells high in PLK1 were killed or prevented from growing. Notably, inhibiting PLK1 did not harm normal brain cells.

Dr. Sandra Dunn’s co-authored paper, Polo-like kinase 1 inhibition kills glioblastoma multiforme brain tumor cells in part through loss of SOX2 and delays tumor progression in mice, was published in the journal Stem Cells.

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Stopping Cancer Cells from SpreadingCFRI scientists have revealed more about a molecular pathway that controls cell movement, opening a new route for drugs aimed at keeping cancerous cells from spreading. The researchers focused on rhabdomyosarcoma, the most common form of soft-tissue cancer in children. In the past five years, almost 20 children with the disease have been treated at BC Children’s Hospital, among the thousands of Canadian kids who develop related cancers annually.

According to the study led by the MCCCRP’s Dr. Catherine Pallen, a key link in cell movement is the activity of a protein called PTPa. Her group previ-ously showed that it is possible to stop cells in their tracks by preventing PTPa from being activated by gaining an additional molecular modification called a phosphate group.

The CFRI group has now discovered that PTPa is the ringmaster for at least three proteins, which together regulate cell movement. When PTPa gains a phosphate group, it attaches to a cell’s interior edge. There it acts as an anchor and binding site for two other proteins – BCAR3 and Cas – critically positioning the latter to promote cell movement. In ongoing research, Dr. Pallen’s team has confirmed that this protein trio is active in cancer cells, and that disrupting this molecular pathway stops the cancerous movement of rhabdomyosarcoma cells.

Dr. Pallen’s co-authored paper, PTPa Phosphotyrosyl-789 Binds BCAR3 to Position Cas for Activation at Integrin-Mediated Focal Adhesions, was published in the journal Molecular and Cellular Biology.

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Best Treatment When Bone Marrow FailsOur researchers have shown that children with a life-threatening form of bone marrow failure can be effectively treated without a bone marrow transplant.

Every year, several children in BC and several hundred across North Amer-ica develop acquired aplastic anemia (AA), a condition in which a person’s bone marrow stops producing enough new blood cells. Until now, a bone marrow transplant from a sibling was the preferred treatment. However, most children don’t have a compatible sibling, and there are significant potential complications related to transplantation.

MCCCRP-funded researchers Dr. Kirk Schultz and Dr. Rebecca Deyell, and their research team at the CFRI, recently reported that a medication-based treatment called immunosuppressive therapy appears to be as successful as bone marrow transplants in treating AA. The scientists mined BC Chil-dren’s Hospital’s comprehensive database to analyze the outcomes of 45 children, ages one to 17, treated for AA with immunosuppressive therapy at the hospital between 1991 and 2008. The study found that their sur-vival rate was 96 per cent after five years, and 90 per cent after 10 years – similar to that of transplant recipients. The study also called into question the need for the use of a bone marrow growth factor medication, thought by some to speed recovery in AA patients, but also associated with higher rates of relapse.

Dr. Schultz and Dr. Deyell’s paper, Immunosuppressive therapy without hematopoietic growth factor exposure in pediatric acquired aplastic anemia, was published in The Journal of Pediatric Hematology and Oncology.

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LEVERAGE FOR THE GREATER GOODChildhood Cancer & Blood Research BioBankWith your support, the MCCCRP has established the Childhood Cancer & Blood Research BioBank – the first childhood cancer bank in the province – at BC Children’s Hospital. The BioBank relies on biological donations from children and youth who are being treated for cancer or blood disorders at BC Children’s Hospital. Patients at Children’s who choose to donate samples or information to the BioBank have the option to donate their samples for local research only, or for larger national and international research projects.

Although significant scientific discoveries can be made in the test tube with externally-acquired cancer cell samples, cells that come directly from current patients at BC Children’s enable researchers to examine real-world characteristics of pediatric cancer cells. This leverages their ability to translate exciting scientific discoveries into new targeted therapies for children being treated for cancer at the hospital, which depends heavily on the evaluation of those therapies against cancer derived from real patients. This is a critical component of the preclinical testing stage and is required before potential therapies can be evaluated in human clinical trials.

The first patient donated a tumour sample to the BioBank in September 2011. Since then, more than 70 participants have donated biological samples. These samples are essential to develop researchers’ understand-ing of pediatric cancer, to improve future treatments and to find a cure.

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Your support toward the cancer-specific BioBank is keeping the MCCCRP on the leading edge of child-health research, and also attracting addition-al research funds to help all children and families who may benefit from this innovative resource. The BioBank has captured the interest of researchers across the CFRI and other institutions, both locally and internationally. Its success has demonstrated the profound need to build an institutional BioBank to serve the needs of researchers across all disciplines within the CFRI. The attention generated from the Childhood Cancer & Blood Research BioBank has been key in providing the case for expanding this resource and, as such, your support has leveraged an additional donation to create an institutional BioBank.

Funding GrantsThe MCCCRP has consistently been awarded grants to further its research goals. Last year, the program was awarded $2.1 million in operating grants and $482,401 in grants for equipment. Acquiring grant funding is critical to the program. It allows promising childhood cancer research to progress at a much faster pace, and it advances the translation of scientific discov-eries into new and enhanced treatments for children with cancer. It also enables the MCCCRP to continue to recruit the best and brightest research scientists to the program and to leverage additional funding from other granting bodies.

Having a stable source of funding to support researchers, their projects and labs, is what enables the CFRI to win these grants. Your support is critical to our success and continues to leverage the resources needed for the MCCCRP to excel.

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Publication of Research FindingsResearchers in the MCCCRP have contributed to the world-wide childhood cancer research community by collaborating with other program researchers and publishing papers in peer-reviewed journals.

Number of publications of MCCCRP researchers and their collaborators from 2010-12

FellowshipsThe MCCCRP is committed to fostering the training and advancement of scientists to further Michael’s vision of a future without childhood cancer. Michael Cuccione Fellowships were established more than 10 years ago and have a $1.5-million endowment, which generates approximately $60,000 per year.

In November 2012, the Michael Cuccione Fellowship Endowment for Oncology Research was revised to reflect the additional need to offer one to three graduate studentships to masters or doctoral students on a recurring basis. These bright, young individuals are the future pioneers of childhood cancer research and provide critical support for the research activities of MCCCRP investigators. With the support of the Michael Cuccione Foundation, the MCCCRP can guarantee that funds will be available to hire one or more of the talented trainees who will one day become the custodians of today’s research.

The Michael Cuccione Fellowship Endowment for Oncology Research grant application deadline is on May 15, 2013. We look forward to sharing more information with you about the promising research personnel and projects you are supporting in the year to come.

0 5 10 15 20

11 / Leukemia/LymphomaBond, Lim, Maxwell, Rassekh,

Reid, Schultz, Veracautern

19 / Brain TumourDunham, Dunn, Hukin,

Maxwell, Pallen, Rassekh

12 / SarcomasBond, Brown,

Pallen, Sorensen

2 NeuroblastomamphomaDeyell, Maxwell, Reid

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LOOKING FORWARDThanks to the Michael Cuccione Foundation’s support of research leadership, fellowships, programs, projects and labs, you are helping the MCCCRP to remain on the forefront of medical science and childhood cancer discovery.

In 2013-14, $400,000 of MCCCRP funding will go toward a Pediatric Brain Tumour Project research fund. These funds will support innovative research initiatives and collaborations that advance knowledge of brain tumour biology but have no other sources of funding. These start-up funds may also be used to gather preliminary data that will form the basis for future grant applications to other funding agencies. Each approved project will receive funding for a maximum of two years.

The application deadline for this funding opportunity is on May 1, 2013. We look forward to reporting back to you about the projects that will be funded through your support.

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THANKYOU!

Your generosity is making a difference in the lives of children and families living with cancer across our province. Thanks to your support, researchers in the Michael Cuccione Childhood Cancer Research Program are making breakthrough discoveries in the fight against this devastating disease. Their findings are leading to innovative treatments that are improving – and saving – the lives of kids with cancer. Together we are working to create a world without childhood cancer and, in honour of Michael’s dream, we are making a difference.

“One person can only do so much, but together we can make a difference.” —Michael Cuccione

BC Children’s Hospital Foundation938 West 28th Avenue, Vancouver BC V5Z 4H4Tel: 604 875 2444 Toll Free: 1 888 663 3033Fax: 604 875 2596 www.bcchf.ca