Dec. 12, 2007 Oregon Health & Science University Cancer Institute researcher Jeff Tyner, Ph.D., has created a way to identify proteins that are candidates for targeted therapy in acute myeloid leukemia using an assay that yields results in just four days. This research is being presented at the American Society of Hematology annual meeting in Atlanta, on Dec. 10.
This functional assay, called RAPID, because it rapidly delivers the information, has the capability of telling researchers which actual proteins from the tyrosine kinase family are contributing to an individual patient's cancer.
"If you know what protein is driving the cancer, you have the ability to target that protein and stop it. With this knowledge it may be possible to match targeted drugs with the appropriate patient. It may also be possible to identify mechanisms as to why certain leukemias respond well to therapy and why others may not. The real novelty of our work is that we have performed this assay directly on patient samples. It gets us one step closer to the clinic and personalized medicine," said Tyner, a fellow in hematology/ medical oncology, OHSU School of Medicine.
This research has several important aspects. First, it will enable researches to more quickly compile a database of mutant genes that cause cancer. That will enable better diagnosis in the future using DNA sequencing technology. Second, it is possible that this technology may, in the future, be adapted for direct clinical use for diagnostic purposes. In this manner, the RAPID screen could be run on a patient's malignant cells, and the appropriate drug could then be determined to treat that patient. Thirdly, the assay can be completed in just four days, whereas previous technologies could take months to years to yield similar information.
Tyner came about his discovery as many scientists do: trial and error and then success.
"We were initially screening for these targets by doing large-scale DNA sequencing, looking for mutations. This strategy was not as successful as we had hoped, so we decided that an assay that could functionally screen cells and give us some idea based on what killed cells and what didn't kill cells would be a better place to start. We could then work backward to find the actual mutation underlying that phenotype. RNAi (the name of the technology we use) seemed an ideal platform for this because it allows you to knock down the expression of individual genes," Tyner said.
Acute myeloid leukemia is a cancer characterized by the rapid proliferation of abnormal cells which accumulate in the bone marrow and interfere with the production of normal blood cells. This leukemia is the most common acute leukemia affecting adults, and its incidence increases with age. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated. About 9,000 deaths from AML will occur in the United States during 2007.
Other researchers include: Stephanie Willis, research associate, division of hematology and medical oncology, OHSU School of Medicine; Michael Deininger, M.D., Ph.D., assistant professor of medicine, division of hematology and medical oncology, OHSU School of Medicine; and Brian Druker, M.D., OHSU Cancer Institute Director, JELD-WEN Chair of Leukemia Research at the Oregon Health & Science University Cancer Institute, Howard Hughes Medical Institute Investigator and a member of the National Academy of Sciences.
OHSU has licensed some of the underlying technology used in this research to MolecularMD.
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