Cancer research at the Children’s Hospital of Eastern Ontario

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Despite the numerous advances made in the fight against cancer, despite the fact that today more children survive cancer than ever before, it is still far too prevalent and it affects far too many people.

Researchers, staff and trainees alike at the Children’s Hospital of Eastern Ontario (CHEO) Research Institute share a common goal: to make cancer a thing of the past. It’s what fuels us as we look for ways to not only cure cancer but to also make treatments easier on patients.

Because cancer is a nemesis that has one name but many faces – there are in fact well over 100 different types of cancer – CHEO researchers are looking at it from different angles; for example, some consider biology by analyzing tumor biopsies, while others address treatment options by looking at what timing is optimal for administering chemotherapy, and others look at supportive care to see if acupuncture helps to alleviate nausea, in the hope this will eliminate some of the side effects of existing treatments.

CHEO is also a member of the Children’s Oncology Group (COG) which aims to understand the causes of cancer and find more effective treatments for children. As part of this international research network, our clinical cancer researchers have access to funding, treatments, research support and services specifically aimed at better outcomes for pediatric cancer patients. Dr. Jacqueline Halton is the Canadian Senior Medical Officer for COG, making her responsible for securing approval to use novel cancer treatments in Canada and at CHEO; this allows physicians to offer each oncology patient in their care the opportunity to take part in a clinical trial, if one is available for their particular type of cancer and seems like a promising course of treatment.

Many other CHEO oncologists are pursuing research interests, independent of the COG network. Dr. Donna Johnston, Chief, Division of Hematology/Oncology at CHEO, Dr. Jacqueline Halton, Dr. Robert Klaassen, Dr. Karen Mandel, Dr. Raveena Ramphal, Dr. Mylène Bassal, and Dr. Ewurabena Simpson, are individually collaborating on 36 multi-centre studies ranging in topics from evaluating the cardiac late effects in childhood cancer survivors; to looking at central line dysfunction in children with cancer; to applying biomarkers to long term effects of childhood/adolescent cancer treatment; and to equipping patients with iPhones to record their pain scale.   “We are extremely proud that our researchers are leading projects that have the potential to change cancer treatments on an international scale,” says Dr. Martin Osmond, CEO and Scientific Director, CHEO Research Institute.

Another instance is Dr. Johnston’s phase one clinical trial to determine what dose of melatonin, a natural health product, is tolerable by pediatric cancer patients when it is used as an appetite stimulant.  Dr. Klaassen, for his part, has recently launched a trial to validate a new myelodysplasia-specific measure of quality of life. This scale was developed thanks to input from patients, caregivers, healthcare providers and quality of life experts and aims to assess the impact of myelodysplastic syndromes, a blood disorder with low blood counts and a high risk of cancer, on a patient’s quality of life.

Meanwhile, Dr. Leanne Ward is focusing her research on the bone health of our children, since children with leukemia have the potential to develop osteoporosis, a serious bone disorder causing fractures of the spine as well as other parts of the skeleton (such as the arms and legs).  She is presently leading a study to define how often osteoporosis occurs in children with leukemia, to look at what is the profile of the child most likely to develop osteoporosis, and to assess the potential for recovery. Ultimately, her goal is to identify osteoporosis as early as possible, and to develop best treatment and prevention strategies for this complication of childhood leukemia.

Concurrently, recent developments in CHEO’s laboratories have provided us with better insight into the biology of cancer cells. Indeed, our esteemed scientists are looking at cancer research from an altogether different standpoint: Dr. David Stojdl has found a way to trick resistant cancer cells into committing suicide following oncolytic virus therapy. Oncolytics are cancer-killing viruses, so oncolytic virology uses live viruses to sense the genetic difference between a normal tumor and a normal cell. This means that once the virus finds a tumor cell, it replicates inside that cell, kills it and spreads to adjacent tumor cells to seed a therapeutic ‘chain reaction.’

His success in mouse models is the beginning of a laborious journey that should see this discovery tested in clinical trials in a couple of years. This type of therapy is far less toxic for children than the traditional oncology treatments of radiation and chemotherapy, meaning there would be fewer toxic side effects, and more importantly, fewer chances of cancer reoccurring in adulthood.   Dr. Robert Korneluk and his team are studying targeted anti-cancer therapies that will complement existing treatments by providing a safer, more effective way to kill tumor cells.  Dr. Korneluk is currently exploring ways to combine new tumor-killing virus therapy with experimental ‘anti-IAP’ drugs. IAP is short for ‘inhibitor of apoptosis’ and represent a family of genes that are central to the survival of cancer cells. They are also essential to immunity, making them ideal drug targets.

These anti-IAP drugs induce the specific death of cancer cells and further sensitize them to killing by the immune system, which is often triggered by anti-cancer viruses. The drug effect is further enhanced when the tumors are infected with the virus. This combination approach, Dr. Korneluk believes, will eventually become an effective and safe treatment for a variety of cancers, including those that affect children.

Importantly, both of these new experimental anti-cancer therapies are not “genotoxic,” meaning they do not damage DNA or kill normal dividing cells, as current cancer therapies do. Therefore, the overall quality of life of children with cancer undergoing treatment, or childhood cancer survivors, should improve with the use of these new agents.

Another exciting project is that of Dr. Martin Holcik and his team. They have identified new ways to control expression of several key regulators of cell death and survival. His work is focused on the investigation of the regulation of protein synthesis (translation), with specific emphasis on selective translation of specific factors during pathophysiological cellular states such as cellular stress, apoptosis (cell death) and cancer. Specifically, his team is investigating why and how cancer cells turn on genes that allow cancer cells to survive and thrive despite radiation or chemotherapy.

It takes energy, passion and commitment to investigate better treatment options and new cures for cancer. At the CHEO Research Institute we aim to make discoveries today for healthier kids tomorrow.  Because kids should be kids… not patients.

For more information about the CHEO Research Institute, please visit www.cheori.org