New Study on Why Cells Resist Chemotherapy Provides New Treatments for Childhood Cancer
April 05, 2007
VANCOUVER, April 2007 (Source: BC Cancer Agency)—A new way of looking at what makes childhood cancers resistant to treatment has given researchers at the BC Cancer Agency potential new targets for chemotherapy. Published in the journal Cancer Research this month, Dr. Poul Sorensen’s study found that cells from a common childhood cancer behave much differently when placed in liquid suspension compared to how they grow in solid tissues.
It’s an important discovery, because one of the great challenges in treating childhood cancer is metastasis – when cancer cells break away from the original tumor and travel through the blood or other fluids to form secondary tumors at another site in the body. Most childhood solid tumor deaths are a direct result of such metastatic spread of disease.
“We believed that the cells would behave differently when they are in a different environment,” says Dr. Sorensen, Senior Scientist at the BC Cancer Agency. “So we wanted to see what the properties of the cells are between the time they leave the primary tumor and travel through the blood to arrive at the secondary site.”
Dr. Sorensen took cells from Ewing Sarcomas – the second most common pediatric cancer of bone– and cultured them in a solution mimicking the blood, to recreate the environment such cells would be in while traveling through the body. Usually, cells need to be anchored to a solid mass in order to survive, but in this case, being in suspension caused the cancer cells to grow stronger and to acquire chemoresistant features.
“Normal cells die rapidly in suspension, so whatever the cancer cells do to survive in suspension is likely strongly related to that which makes them resistant to chemotherapy,” explains Dr. Sorensen.
He found that the cells formed small clusters in solution, and that these clusters express a protein called E-cadherin, normally not found in sarcomas. The presence of E-cadherin allows the cell clusters to then activate another protein called ErbB4, a receptor tyrosine kinase that helps to regulate growth in the tumour cells and renders the tumour cells able to resist chemotherapy.
“If you block E-cadherin, you block the activation of ErbB4, and then these cells begin to die and chemosensitivity is restored,” says Dr. Sorensen. “These are proteins we can potentially target for therapy with an antibody or a small molecule inhibitor.”
Dr. Sorensen’s team is already working with pharmaceutical companies to develop such a therapy.
This discovery has implications beyond the treatment of Ewing Sarcoma. The E-cadherin protein is often found in tumour cells of adult epithelial malignancies, and so this could be relevant to the question of why a number of adult cancers become chemo-resistant during metastasis.
“One message that comes out very strongly from these studies is that working on childhood cancer can teach us so much about general oncology, as there is tremendous overlap in the biological pathways that may be involved in each disease group.”
Core support for research at the BC Cancer Agency is provided by the BC Cancer Foundation. Support for this research project was also provided by the Children’s Oncology Group and the Johal Endowed Chair in Childhood Cancer Research through the Children’s Hospital Foundation.
The BC Cancer Agency, an agency of the Canadian Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. For more information, visit the agency's Web site.
<< Back
April 05, 2007
VANCOUVER, April 2007 (Source: BC Cancer Agency)—A new way of looking at what makes childhood cancers resistant to treatment has given researchers at the BC Cancer Agency potential new targets for chemotherapy. Published in the journal Cancer Research this month, Dr. Poul Sorensen’s study found that cells from a common childhood cancer behave much differently when placed in liquid suspension compared to how they grow in solid tissues.
It’s an important discovery, because one of the great challenges in treating childhood cancer is metastasis – when cancer cells break away from the original tumor and travel through the blood or other fluids to form secondary tumors at another site in the body. Most childhood solid tumor deaths are a direct result of such metastatic spread of disease.
“We believed that the cells would behave differently when they are in a different environment,” says Dr. Sorensen, Senior Scientist at the BC Cancer Agency. “So we wanted to see what the properties of the cells are between the time they leave the primary tumor and travel through the blood to arrive at the secondary site.”
Dr. Sorensen took cells from Ewing Sarcomas – the second most common pediatric cancer of bone– and cultured them in a solution mimicking the blood, to recreate the environment such cells would be in while traveling through the body. Usually, cells need to be anchored to a solid mass in order to survive, but in this case, being in suspension caused the cancer cells to grow stronger and to acquire chemoresistant features.
“Normal cells die rapidly in suspension, so whatever the cancer cells do to survive in suspension is likely strongly related to that which makes them resistant to chemotherapy,” explains Dr. Sorensen.
He found that the cells formed small clusters in solution, and that these clusters express a protein called E-cadherin, normally not found in sarcomas. The presence of E-cadherin allows the cell clusters to then activate another protein called ErbB4, a receptor tyrosine kinase that helps to regulate growth in the tumour cells and renders the tumour cells able to resist chemotherapy.
“If you block E-cadherin, you block the activation of ErbB4, and then these cells begin to die and chemosensitivity is restored,” says Dr. Sorensen. “These are proteins we can potentially target for therapy with an antibody or a small molecule inhibitor.”
Dr. Sorensen’s team is already working with pharmaceutical companies to develop such a therapy.
This discovery has implications beyond the treatment of Ewing Sarcoma. The E-cadherin protein is often found in tumour cells of adult epithelial malignancies, and so this could be relevant to the question of why a number of adult cancers become chemo-resistant during metastasis.
“One message that comes out very strongly from these studies is that working on childhood cancer can teach us so much about general oncology, as there is tremendous overlap in the biological pathways that may be involved in each disease group.”
Core support for research at the BC Cancer Agency is provided by the BC Cancer Foundation. Support for this research project was also provided by the Children’s Oncology Group and the Johal Endowed Chair in Childhood Cancer Research through the Children’s Hospital Foundation.
The BC Cancer Agency, an agency of the Canadian Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. For more information, visit the agency's Web site.
<< Back
