title: The one-two punch: combination treatment in chronic myeloid leukemia.
abstract: Despite the success of tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML), minimal residual disease persists, requiring indefinite treatment. Accumulated evidence has shown that leukemic stem cells (LSCs) in the bone marrow can survive TKI treatment via downstream BCR-ABL1-independent signaling pathways that are activated by soluble growth factors and interactions with the extracellular matrix in the bone marrow microenvironment. Research efforts have therefore turned to the identification and development of agents that target LSCs, and together with TKIs, have the potential to eradicate CML. A number of such agents are now under clinical investigation, and others are soon to enter early-phase studies. This review examines the pathways, molecular targets, and potential new therapeutics that, with TKIs, may provide an effective "one-two punch" to cure CML.
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, 13131 Magnolia Drive, 3 East, Rm 3056H, Tampa, FL 33612, United States.
authors: Kendra L
authors: KL
authors: Sweet
authors: Lori A
authors: LA
authors: Hazlehurst
authors: Javier
authors: J
authors: Pinilla-Ibarz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D053612:Janus Kinases; D058570:TOR Serine-Threonine Kinases; D054648:Protein Phosphatase 2
keywords: Chronic myeloid leukemia; Dasatinib; Imatinib; Leukemic stem cells; Nilotinib; Tyrosine kinase