ArticleFrontiers in oncology2020
DNA-PK Inhibitor, M3814, as a New Combination Partner of Mylotarg in the Treatment of Acute Myeloid Leukemia.
Article in Frontiers in oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting Artemis Sensitizes B Cells to Topoisomerase 2 Poisons by Disrupting DNA-PKcs-Dependent Repair.Research square · 2025Article
- DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications.Nature reviews. Drug discovery · 2025Review
- Exploring the role of PARP1 inhibition in enhancing antibody-drug conjugate therapy for acute leukemias: insights from DNA damage response pathway interactions.Journal of translational medicine · 2024Article
- Article
- Discovery of the DNA-PKcs inhibitor DA-143 which exhibits enhanced solubility relative to NU7441.Scientific reports · 2024Article
- Cocaine-induced DNA-PK relieves RNAP II pausing by promoting TRIM28 phosphorylation.bioRxiv : the preprint server for biology · 2024Article
- Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma.Molecular cancer therapeutics · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- AZD-7648, a DNA-PK Inhibitor, Induces DNA Damage, Apoptosis, and Cell Cycle Arrest in Chronic and Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2023Article
- Review
- DNA damage accumulation and repair defects in FLT3-ITD acute myeloid leukemia: Implications for clonal evolution and disease progression.Hematological oncology · 2023Review
- Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer.BMC cancer · 2022Article
- Article
- Article
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2021Article
- Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.Experimental hematology & oncology · 2021Review
- Review
- DNA-PK inhibitor peposertib enhances p53-dependent cytotoxicity of DNA double-strand break inducing therapy in acute leukemia.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite significant advances in the treatment of acute myeloid leukemia (AML) the long-term prognosis remains relatively poor and there is an urgent need for improved therapies with increased potency and tumor selectivity. Mylotarg is the first AML-targeting drug from a new generation of antibody drug conjugate (ADC) therapies aiming at the acute leukemia cell compartment with increased specificity. This agent targets leukemia cells for apoptosis with a cytotoxic payload, calicheamicin, carried by a CD33-specific antibody. Calicheamicin induces DNA double strand breaks (DSB) which, if left unrepaired, lead to cell cycle arrest and apoptosis in cancer cells. However, repair of DSB by the non-homologous end joining pathway driven by DNA-dependent protein kinase (DNA-PK) can reduce the efficacy of calicheamicin. M3814 is a novel, potent and selective inhibitor of DNA-PK. This compound effectively blocks DSB repair, strongly potentiates the antitumor activity of ionizing radiation and DSB-inducing chemotherapeutics and is currently under clinical investigation. Suppressing DSB repair with M3814 synergistically enhanced the apoptotic activity of calicheamicin in cultured AML cells. Combination of M3814 with Mylotarg in two AML xenograft models, MV4-11 and HL-60, demonstrated increased efficacy and significantly improved survival benefit without elevated body weight loss. Our results support a new application for pharmacological DNA-PK inhibitors as enhancers of Mylotarg and a potential new combination treatment option for AML patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.