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Our knowledge of cancer initiation, progression and §treatment has dramatically increased over the last §decade. This understanding promises to deliver §novel therapeutic agents that will eliminate the §burden of the disease on individuals, families and §society. However, early impressive clinical results §are often overshadowed by relapse and the §development of resistance. Recent studies strongly §support the notion that at least some cancers are §initiated, maintained and disseminated by cancer §stem cells. These cells possess properties of normal §stem cells and are typically less responsive to §current therapies, thus explaining the observed §resistance. Based on the cancer stem cell theory, §the elimination of these cancer stem cells §is imperative if we are to cure patients. A number §of aberrantly activated proteins have been found §critical for the proliferation and/or survival of §cancer stem cells, one of which is the mutant FLT3 §receptor, expressed on leukemia stem cells. This §book uses FLT3 as an example to illustrate the §development of targeted therapeutics, mechanisms of §resistance and strategies to overcome resistance.