Research ArticleCancer

PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL+ human leukemia

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Science Translational Medicine  07 Feb 2018:
Vol. 10, Issue 427, eaan8735
DOI: 10.1126/scitranslmed.aan8735

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Drug pair enABLes killing of leukemia

Imatinib, the classic targeted drug for the treatment of cancer, was designed to target the BCR-ABL fusion protein in chronic myeloid leukemia and has saved many patients’ lives. Unfortunately, some leukemias are resistant to imatinib despite having the BCR-ABL translocation, and others can develop resistance during treatment. Moreover, imatinib generally does not eradicate the leukemic stem cells and therefore requires continued treatment to maintain efficacy, so combination approaches are still needed. Lai et al. discovered that protein phosphatase 2A is a therapeutic target in imatinib-insensitive leukemia cells, including stem cells, and that the combination of imatinib and related drugs with PP2A inhibition effectively kills these cancer cells.