2014 Research Grant Winner

The Cancer Research Society, in partnership with Carcinoid NeuroEndocrine Tumour Society of Canada (CNETS Canada) is awarding $120,000 to Dr. Trevor Pugh and his team of researchers from University Health Network, located in Toronto, to continue their study on gastrointestinal and pancreatic neuroendocrine tumours. Their research aims to find a molecular signature that would identify patients who could benefit from a group of drugs called mTOR inhibitors.

Well-differentiated neuroendocrine tumours belong to a group of rare cancers that are incurable once they have metastasized and are not amenable to surgery. An alternative treatment option is conventional chemotherapy but it has been shown to have limited effect on these neuroendocrine tumours. A more targeted approach is the use of a group of drugs called mTOR inhibitors that have shown anticancer activity in patients with advanced pancreatic cancer.

« Our goal is to find a molecular signature that would allow us to distinguish the patients who would benefit from mTOR inhibitors from those who would not. With this objective, we are sequencing the DNA and RNA of each gene in the tumours of patients while they are undergoing treatment with an mTOR inhibitor, and comparing this data to tumours removed prior to treatment. This will allow us to observe the genes that change in response to the treatment. These results will help us to understand how neuroendocrine tumours act during treatment, and the goal will be to lead to new ways to adapt the treatment of these types of cancer and others that are treated with similar medications, » explained Dr. Pugh. “The support of CNETS Canada and the Cancer Research Society comes at a very timely point in neuroendocrine tumour research and treatment, as genome profiling and treatment with targeted therapies are maturing to have major impact on treatment of patients. Our study brings together clinical and basic research teams to observe genetic changes of neuroendocrine tumours in patients undergoing active treatment with targeted therapies. Such knowledge will enable physicians to select patients most likely to benefit from mTOR inhibitors and expedite alternative treatments in patients unlikely to respond,” added Dr. Pugh.

« Our collaboration with CNETS Canada aims to support the launch of an important project for research into new options for the treatment of neuroendocrine tumours, », stated Andy Chabot, President and Chief Executive Officer of the Cancer Research Society. «We want to be proactive and make every effort to find solutions for this type of cancer, which has a five-year survival rate of approximately 40%. »

« We hope that this research will lead to new treatment options in the very near future directly for the patient community that worked so hard to raise these funds, » stated Jackie Herman, President of CNETS Canada. « With so few neuroendocrine specific research projects underway in Canada, we are delighted to be in a position to partner with the Cancer Research Society in support this project and are very optimistic, expecting significant outcomes, » added Ms. Herman.

The Cancer Research Society is a national not-for-profit organization whose sole mission is to fund research on all types of cancer, thereby contributing to the advancement of science aimed at preventing, detecting, and treating this disease. The Cancer Research Society is devoted to both basic research, which has resulted in several innovative discoveries, as well as environment-cancer, a field in which the Society is considered to have played a pioneering role in Canada. During the past five years, the Cancer Research Society has granted over $ 41 million to some 283 cancer research projects across the country through diverse fundraising activities. For more information on cancer, on the Cancer Research Society or to support research, visit www.CancerResearchSociety.ca or call 1 888-766-2262.

2013 Research Grant Winner

The Cancer Research Society, in partnership with CNETS Canada, is awarding $120,000 to Dr. Nahum Sonenberg and his team of researchers from McGill University to pursue new ways to treat pancreatic neuroendocrine tumours, the second most common type of cancer affecting the pancreas.

Dr. Sonenberg’s study will expand on progress initially made in 2011 in a previous study jointly funded by the Cancer Research Society and CNETS Canada.

“In 2011, we worked with two pharmacological compounds (Everolimus and Sunitinib) that were reported to significantly increase the survival of patients with pancreatic neuroendocrine tumours by blocking cancer growth and spread,” stated Dr. Sonenberg. “These drugs act in shutting down a hyperactivated major pathway that increases the protein synthesis required for proliferation and metastatic properties, thereby limiting the cancer’s ability to progress. By gaining a clearer understanding of how this process works, we are hoping this will lead to the identification of additional targets for new treatment developments,” added Dr. Sonenberg.

Neuroendocrine tumours are difficult to detect because they can occur almost anywhere in the body and progress very slowly, with symptoms that can vary enormously or be confused with those of other illnesses, with some patients reporting no symptoms at all. This can result in patients being diagnosed only at an advanced stage, when tumours have grown and spread, requiring a regimen of severe chemotherapy which is often unsuccessful.

Despite significant advances in the treatment of other cancers, neuroendocrine tumours remain very difficult to diagnose and treat. CNETS Canada is committed to advancing research into neuroendocrine tumours while the Cancer Research Society’s goal is to fund the most innovative and scientifically sound research projects in Canada, addressing all types of cancer. This partnership aims to combine efforts and resources and build a comprehensive research community in order to make significant breakthroughs.

“We hope that this research will lead to new treatment options for patients in the near future,” stated Jackie Herman, President of CNETS Canada. “All parties involved in this partnership are optimistic, expecting significant outcomes,” added Ms. Herman. Right now, surgery offers the only chance for a cure for neuroendocrine tumours, but only a small percentage of patients are diagnosed early enough to be eligible.

“We are very excited about the research made possible by our partnership with CNETS Canada, because it will likely contribute to finding new ways to treat pancreatic neuroendocrine tumours and hopefully save lives,” stated Mr. Andy Chabot, President and Chief Executive Officer of the Cancer Research Society.

The Cancer Research Society is a national not-for-profit organization whose sole mission is to fund research on all types of cancer, thereby contributing to the advancement of science aimed at preventing, detecting, and treating this disease. The Cancer Research Society is devoted to both basic research, which has resulted in several innovative discoveries, as well as environment-cancer, a field in which the Society is considered to have played a pioneering role in Canada. During the past five years, the Cancer Research Society has granted over $ 41 million to some 283 cancer research projects across the country through diverse fundraising activities. For more information on cancer, on the Cancer Research Society or to support research, visit www.CancerResearchSociety.ca or call 1 888-766-2262.

2012 Research Grant Winner

Dr. Lois Mulligan of the Cancer Research Institute at Queen’s University, in Kingston, Ontario, was awarded the 2012 research grant for her outstanding research proposal entitled “Isoform-specific regulation of the RET receptor tyrosine kinase”.

Here is a lay person’s understanding, explained by one of CNETS Canada’s Medical Experts.

Every single cell in our body is a marvelous, astonishing and unrivaled piece of engineering. All aspects of the life of a cell are tightly controlled by intricate and complex molecular mechanisms. One of the major characteristics of most cells in our body is to grow and duplicate themselves in response to the needs of our organs and our body. The cellular mechanisms that control these two functions are critically regulated by very specific messengers and signals. These can be simplistically categorized into three categories: those which tell the cell to reproduce called “oncogenes”; those that slow down cell division called “tumor suppressor” genes and finally those that trigger the death of the cell, also called apoptosis, when the genome of the cell has been irrevocably damaged. Alteration of any of these signals has the potential to generate a significant deregulation of the cell and can result in its uncontrolled growth and tumor formation.

Dr. Mulligan’s successful research proposal will shed light on the function and regulation of one of the growth signals (RET) described above that has been shown to be deregulated in patients with a form of neuroendocrine tumor called MEN2 (multiple endocrine neoplasia type 2). MEN2 is characterized by the development of medullary thyroid carcinoma (MTC), bilateral pheochromocytoma and parathyroid hyperplasia (MEN2A) and mucosal neuromas (MEN2B).

We believe that Dr. Mulligan’s outstanding research proposal on the characterization of cellular trafficking of the RET proto-oncogenes will lead to a better understanding of the role of the RET proteins in NETs. It will also enable a better understanding of the complex regulation of the cellular mechanisms of normal and cancer cells. We believe that Dr. Mulligan’s research could lead to the development of novel personalized therapies.

The Cancer Research Society is at http://www.src-crs.ca/en-CA

2011 Research Competition Winner

Dr. Nahum Sonenberg of Mc Gill University in Montreal, Quebec, Canada was awarded the 2011 research grant.

Dr. Sonenberg is a highly respected researcher within the Canadian research community.

Here is Dr. Sonenberg’s summary. mTOR inhibition and translation control of pancreatic neuroendocrine tumours.

Layman Summary: Pancreatic neuroendocrine tumours are the second most common malignancy of the pancreas with a five-year survival rate of approximately 40%. Patients are often diagnosed with extensive metastasis and therefore must embark on a severe chemotherapeutic regimen that showed limited efficacy. There is a need for novel systemic therapies and this past week (Feb 10, 2011) brought exciting news:

The compound Everolimus was just reported to significantly increase the progression-free survival of patients affected with pancreatic neuroendocrine tumours. Everolimus acts by shutting down a molecular pathway that is often found hyperactivated in pancreatic neuroendocrine tumours, the mTOR pathway. This past year, several novel second-generation inhibitors of mTOR were discovered, and they demonstrated a much higher efficacy in inhibiting this pathway as well as greater anti-cancer properties.

Our goal is to assess the novel active-site inhibitors of mTOR in pancreatic neuroendocrine tumours. By using a biochemical, genetic, and animal model approach, we aim to elucidate the mechanisms by which mTOR, and its downstream effectors, regulate neuroendocrine tumour progression. Furthermore, we will identify novel biomarkers that act on this disease and predict response to therapeutic inhibition of the mTOR pathway. Our study will provide insightful information for the treatment of pancreatic neuroendocrine tumors using mTOR inhibitor compounds.

2010 Research Grant Award

CNETS Canada – Cancer Research Society- Carcinoid-NET Research Grant was awarded in 2010 to Dr Herman Yeger ( Hospital for Sick Children, Toronto) and research is ongoing.

Dr Herman Yeger of The Hospital for Sick Children, Toronto, is working with Dr Ernest Cutz, also of the Hospital for Sick Children, Ontario on this project., They will carry out research primarily on Lung Carcinoid Tumours. The topic is:

” The Role of Hypoxia/Hypercapnia Chemosensing in the Pathophysiology and Malignant Transformation of Carcinoids “

Lay summary:

Lung neuroendocrine tumors (NET) or carcinoids constitute 1% of all lung cancers. Patients with metastatic carcinoid disease have a poor 5-year survival of 14-25%. Lung carcinoids originate from lung neuroendocrine cells (PNEC). Knowledge about the basic biology of lung NET is incomplete. We first described PNEC and their role as key airway oxygen sensors. PNEC produce the chemical serotonin (5-hydroxytryptamine, 5-HT), responsible for carcinoid syndrome, a major cause of morbidity in patients. We found that 5-HT secretion is induced by low oxygen and high carbon dioxide/acidosis. We found that lung carcinoids express carbonic anhydrases (CA), proteins specialized in sensing carbon dioxide. One CA subtype, CAIX, is up-regulated by low oxygen and high carbon dioxide/acidosis, conditions correlating with tumor aggressive behavior and metastasis. We found that the drug, acetazolamide, a blocker of CA activity, inhibits 5-HT secretion from carcinoid cells. We postulate that CAIX plays a key role in the malignant behavior of carcinoids. We will investigate how carcinoids sense oxygen and carbon dioxide and provide proof-of-principle evidence in an animal model that therapeutic targeting of CAIX with drugs can abolish the carcinoid syndrome and eliminate malignant transformation.