Jamie Michelle Keck, PhD, Senior Research Associate, Knight Cancer Institute
Cathy and Jim Rudd Career Development Award for Cancer Research
Title: "Validation of Ras Pathway Mutations as Potential Drivers of Leukemic Progression"
Abstract: Leukemia is a cancer of blood cells. Many types of leukemia are still treated with standard chemotherapies which have been used for many years until a breakthrough in treatment occurred over 10 years ago for patients with Chronic Myelogenous Leukemia (CML). This treatment used a chemical inhibitor that blocked activity of a mutant fusion protein kinase called BCR-ABL, which drives cancer growth. Kinases are enzymes that add modifications on other proteins to regulate their function or cellular localization. This specific inhibitor blocks ABL kinase activity, eradicates leukemia cells, and restores patient health. Although many leukemias are not driven by BCR-ABL, all cancers have one or more mutations in their DNA that are important for driving uncontrolled cell growth. Many of these mutations affect kinase activity and/or activate growth-promoting pathways. We have begun an ambitious project to sequence all kinase and kinase-associate genes in 190 patient samples to determine which genes are mutated and match kinase inhibitors that effectively block uncontrolled cell growth. Using this approach, we have identified mutations in three proteins that have the potential to drive leukemogenesis through a pathway known to be deregulated in many types of cancer. Our goals are to determine: 1) if additional mutations in these genes identified in patient samples can also drive cell growth; 2) how these mutations contribute to deregulated cell growth and 3) which kinase inhibitors would be effective for treatment. Our hope is to offer personalized alternatives to chemotherapy for patients harboring these driver mutations in the future.