At the American Association for Cancer Research's annual meeting in Chicago this week, St. Jude Children's Research Hospital's Richard Gilbertson used his experience in studying ependymomas — tumors of the central nervous system — to emphasize the importance of genomics in cancer research. Ependymomas can occur in both children and adults, in either the spine or in the brain. But an adult with an ependymoma in the spine has a significantly better prognosis than a child with an ependymoma in the brain, Gilbertson said. Until now, the same treatments have been offered to all patients, no matter the tissue of origin. Mapping the genomic origin of this tumor type could allow for a deeper dive into the subtypes of the disease and offer strategies for how the subsets of the disease should be treated, he added.
Gilbertson and his colleagues found that the genesis of an ependymoma depends on the right combinations of stem cell types and mutations working together. In work which is not yet published, the researchers identified 82 candidate oncogenes and 40 candidate tumor suppressor genes that could affect a patient's risk for developing an ependymoma. This knowledge could help in the development of new drugs, combination therapies, and individualized regimens, Gilbertson said.
His group's effort have also led to the development of a "clinic of mice" — mouse models of different ependymoma subtypes that can be used to test treatments and assay thousands of existing compounds to see if one of them might treat these tumors. To tackle the problem of screening so many drug compounds, Gilbertson's team also developed a model using zebrafish as hosts for mouse model brain tumors — they take ependymomas from mice and implant them in zebrafish — to test compounds on a larger number of fish at once, compared to mice. The team found that the fish adequately mimic mammalian tumors — they faithfully recapitulate the histology, and the tumors successfully interact with the fish's vasculature, and will metastasize, Gilbertson said. This model could be used to ramp up in vitro drug screening and winnow down the list of possibly useful compounds for a particular cancer subtype. While Gilbertson and his team work with ependymomas, he adds this model could work for many kinds of cancer.
Using this approach, Gilbertson's team found that certain drugs normally used to treat breast cancer and colorectal cancer may successfully treat certain subtypes of ependymomas. His hope, he adds, is that such genomics research can lead to better, and more individualized, treatments for kids with cancer.