Targeting autophagy: a novel anticancer strategy with therapeutic implications for imatinib resistance

Figures & data

Figure 1 Targeting the autophagy pathway in CML. Imatinib-resistant BCR-ABL⁺ CML are sensitive to a therapeutic combination of SAHA, a FDA-approved HDAC inhibitor, and CQ, a FDA-approved anti-malarial agent (Carew et al 2007). Here the overall efficacy of SAHA is thought to be compromised by its induction of the autophagy pathway, which is initiated by the formation of double-membraned autophagosomes from vesicular structures coined the phagophore. Autophagosomes deliver their cargo, bulk cytosolic material and organelles, to the lysosome, which degrades the cargo to provide essential building blocks and energy to the CML cell. The lysosomotropic agent CQ compromises lysosomal functions and thus derails the autophagy pathway, augmenting the killing power of SAHA to overcome imatinib resistance provoked by mutations in BCR-ABL and/or p53 (Carew et al 2007).

Abbreviations: CML, chronic myelogenous leukemia; CQ, chloroquine; HDAC, histone deacetylase; SAHA, suberoylanilide hydroxamic acid.

CarewJSNawrockiSTKahueCN2007Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistanceBlood1103132217363733

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