A team led by R. Keith Humphries, a Professor in the Division of Hematology, will receive $5.9 million over five years from the Terry Fox Foundation (TFF) to find new ways to treat aggressive forms of leukemia by rapidly creating and using laboratory-built models that mimic human acute leukemias.
Keith Humphries
Dr. Humphries, the Director of the Terry Fox Laboratory at the BC Cancer Agency, has been a leader in contributing seminal work on why cures for this disease are hard to achieve. Fewer than one in five adult patients diagnosed with the acute form survive longer than 10 years. Many childhood patients will also not benefit from current treatments.
The New Frontiers Program Project Grants is the flagship program of TFF`s investment portfolio, funding team science and excellence in cure-oriented, biomedical research for nearly three decades. The annual competition is currently overseen by the Canadian Institutes of Health Research in conjunction with the foundation`s national research arm, the Terry Fox Research Institute (TFRI). The funds are raised annually by TFF through its annual Terry Fox community and school runs and invested through the TFRI.
Acute leukemias remain one of the most devastating and costly cancers with less than one in five adult patients surviving 10 years and some childhood patients failing current treatments. Most human leukemias are sustained by a rare subset of “leukemia stem cells” which are often resistant to currently used drugs. Cures thus require treatments that effectively target these leukemia stem cells, ideally with little toxicity for normal cells.
The advent of modern tools that can identify every change in every gene in cells, and that can also determine whether and why every gene is being expressed, is putting this goal within reach. In addition, vast libraries of naturally occurring and synthetic chemicals that can target specific molecules in cells are now available.
Dr. Humphries` group will use genetic engineering tools to create in the lab human models of aggressive leukemia, so that mechanisms of treatment resistance and new drugs and biomarkers can be efficiently analyzed and tested directly and repeatedly in human cells that mimic, but do not rely on, patients’ cells. Three projects will focus on examples of the worst types of leukemia known, develop human models of these and, in concert with two groups of world experts in the molecular analysis of cells, will use these models to search for common therapeutic targets.
“Our program harnesses the power of a research team whose expertise combines normal and leukemic stem cell biology, clinical knowledge and a range of sophisticated technologies to obtain cellular, molecular and genetic features of leukemic cells,“ Dr. Humphries said. “A hallmark of our program is to exploit novel methods to reproducibly engineer in the laboratory models of aggressive leukemias directly from normal human blood forming cells. Such models open a pathway to resolve, with extremely high resolution, the differences between normal and leukemic blood stems cells and, ultimately, to identify novel therapeutic targets.”
Other members of the team include: Connie Eaves, a Professor of Medical Genetics and Vice President, Research at the BC Cancer Agency; Aly Karsan, a Professor of Pathology and Laboratory Medicine; Andrew Weng, an Associate Professor of Pathology and Laboratory Medicine; and Martin Hirst, an Assistant Professor in the Department of Microbiology and Immunology.
“There are, and will continue to be, many unsolved mysteries in cancer research which require the attention of brilliant minds if we are to bring new therapeutics and innovations to the clinic,“ said Victor Ling, TFRI`s president and scientific director, and a Professor of Pathology and Laboratory Medicine at UBC.“We must continue to fuel this groundbreaking work if we are to overcome this disease.”