Research
CNETS Canada /CRS Research Competition Winner
The winner of the CNETS Canada NET Cancer research competition is Dr Nahum Sonenberg of Mc Gill University in Montreal, Quebec, Canada.
Dr Sonenberg is a highly respected researcher within the Canadian research community. The $60,000.00 raised by CNETS Canada in 2010 and early 2011 will be matched by another $60,000.00 from the Cancer Research Society.
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.
Research Links
The following are some links for current research.
Neuroendocrine
- A new diagnostic tool to help the carcinoid cancer patients
Hope for the patients with carcinoid syndrome
A study funded by the Cancer Research Society
Canadian Health Reference Guide - Uppsala Research - Endocrine Tumorbiology
- Uppsala Research Group of Endocrine Oncology
- A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake
Other
- Cancer Research Society
- Canadian Institutes of Health Research
- International Agency for Research on Cancer
- American Association for Cancer Research
CNETS Canada 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.
This award was the result of a joint CNETS Canada-Cancer Research Society (CRS) agreement, which raised $60,000.00 through walks and events for research on the part of the Carcinoid Neuroendocrine Cancer grass roots community. This was matched by an equivalent amount by the Cancer Research Society for a combined amount of $120,000.00.
The recipient, 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.