Funded by the Dick Vitale Gala in memory of Chad Carr
Cancer is the leading cause of disease-related death of children past infancy in North America. All cancers contain mutations in their DNA, but the causes of these mutations are usually not known. This gap in our knowledge negatively impacts patient care: It is difficult to predict how a tumor will change – how it will respond and whether it will come back – if one does not understand why or how it developed in the first place. Recently, our lab and others have shown that some childhood cancers contain a fingerprint which can be used to pinpoint what caused its mutations and when they developed. The identification of these fingerprints, or mutational signatures, is a rapidly evolving area of research that has benefited from new technologies, such as whole genome sequencing. This project will identify mutational signatures in aggressive childhood cancers. We will seek to understand whether cancer- causing mutations have common fingerprints, and if these can be used to select patients that would benefit from ongoing clinical trials.
Many cancers are treated with radiation therapy. Some cancers types are especially hard to treat. One type of cancer that affects the lungs and throat is only cured in about half of cases. Even when drug treatments are added to the radiation therapy, cure rates are not much improved. Also, adding drugs to radiation therapy can make the treatment hard for patients to tolerate. New treatment approaches are needed for these patients.
One new approach that is showing promising results is to give refined treatments that are more precisely targeted to each patient’s cancer. This approach is called Precision Medicine. Precision Medicine has not been used much for the cancer type that affects the lungs and throat. Also, Precision Medicine has not yet been used for radiation therapy. Instead, the standard treatment for these patients continues to be a one-size-fits-all approach.
We expect that the standard one-size-fits-all treatment approach could be replaced by Precision Medicine. The objective of our research is to develop new Precision Medicine approaches for the cancer type that affects the lungs and throat for use with radiation therapy. These new treatments could someday lead to higher cure rates and tolerability of treatment. If successful, our research will lead to new clinical trials that will test these new treatment approaches in cancer patients.
Funded in partnership with WWE in honor of Connor’s Cure
Medulloblastoma is the most common malignant brain tumor in children. Medulloblastoma is really made up of four diseases, of which two types: Group 3 and Group 4 account for the majority of cases. The main tumor ‘lump’ in the brain is called the ‘primary tumor’. The primary tumor can spread (metastasize) to cover other regions of the surface of the brain and spinal cord. Most children who die from medulloblastoma die because the tumor has spread (metastasized) and not due to the primary tumor. The most damaging therapies (radiation) for children with Group 3 and Group 4 medulloblastoma are necessary to treat the metastases.
For the most part, medulloblastoma only spreads to the surface of the brain and spinal cord, and not to other organs. According to the textbooks this occurs when cells drop off the primary tumor, float around in the spinal fluid, and then reattach to the brain or spinal cord and start growing again. There really is no evidence or experiments to support this mechanism, just historical speculation. We have now shown that in fact, medulloblastoma spreads through the blood stream—the cells enter the blood stream, and then home back to the brain and spinal cord where they grow and kill the child.
This new understanding of the metastatic process for medulloblastoma offers fresh opportunities to non-invasively diagnose medulloblastoma in the blood, to prevent the metastatic cascade, prevent the progression of metastases, and decrease the toxicity of therapy for children with medulloblastoma.
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