ArticleCancers2025
DNA Damage Sensing and TP53 Function as Modulators of Sensitivity to Calicheamicin-Based Antibody-Drug Conjugates for Acute Leukemia.
Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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13 authors.
Funding
Abstract
BACKGROUND/
objectivesApproved for treatment of acute leukemia, gemtuzumab ozogamicin (GO) and inotuzumab ozogamicin (InO) are antibody-drug conjugates (ADCs) that deliver a toxic calicheamicin (CLM) derivative. The resistance mechanisms to GO/InO remain incompletely understood.
methodsWe performed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 screen for CLM sensitivity genes, and then performed confirmatory cytotoxicity assays.
resultsSeveral DNA damage pathway regulation genes were identified, most notably
conclusionsThese results support further evaluation of combination therapies with corresponding small-molecule inhibitors (currently pursued for therapy of other cancers) toward clinical testing as novel strategies to increase the efficacy of CLM-based ADCs such as GO and InO.
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