ArticleOncotarget2017
Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy.Frontiers in genetics · 2022Review
- Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Therapeutic Targeting of the Leukaemia Microenvironment.International journal of molecular sciences · 2021Review
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- Article
- Targeting mitotic exit in solid tumors.American journal of cancer research · 2021Article
- The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?Journal of hematology & oncology · 2019Review
- The role of aurora A and polo-like kinases in high-risk lymphomas.Blood advances · 2019Review
- Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition.Blood advances · 2019Article
- Redox-responsive self-assembly PEG nanoparticle enhanced triptolide for efficient antitumor treatment.Scientific reports · 2018Article
- Protein kinase inhibitors for acute leukemia.Biomarker research · 2018Review
- Bortezomib-induced miRNAs direct epigenetic silencing of locus genes and trigger apoptosis in leukemia.Cell death & disease · 2017Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B. Therefore, we tested whether interfering with mitotic slippage through proteasome inhibition arrests and kills AML cells more efficiently during mitosis. We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-derived primary AML cells. In a xenotransplant mouse model of human AML, mice receiving volasertib in combination with bortezomib showed superior disease control compared to mice receiving volasertib alone, highlighting the potential therapeutic impact of this drug combination.
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Registered trials
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 Socratic graph.