, Volume 97, Issue 6, pp 681-682
Date: 12 May 2013

Guest editorial: efficacy of and resistance to molecularly targeted therapy for myeloid malignancies

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The introduction of all-trans retinoic acid (ATRA) and the ABL kinase inhibitors has dramatically improved the prognosis of patients with acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML), respectively. These remarkable clinical successes have proved the principle of molecularly targeted therapy, raising expectations that therapeutic interventions targeting altered molecules will improve outcomes in patients with cancers and hematologic malignancies. A number of targeted agents, such as small molecular compounds and monoclonal antibodies, have already been approved and evaluated in clinical development; however, the accumulation of clinical information has also revealed cases of treatment failure due to resistance. Several mechanisms of resistance to targeted agents, such as mutation or amplification of the targeted gene, up-regulation of P-glycoprotein, activation of other pathways, and pharmacokinetic variability, have been observed in the clinical setting. The pr ...