ArticleCell cycle (Georgetown, Tex.)2014
Therapeutic targeting of Polo-like kinase-1 and Aurora kinases in T-cell acute lymphoblastic leukemia.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Selective Aurora A-TPX2 Interaction Inhibitors HaveJournal of medicinal chemistry · 2024Article
- Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells.Biomolecules & therapeutics · 2023Article
- AURKA and PLK1 inhibition selectively and synergistically block cell cycle progression in diffuse midline glioma.iScience · 2022Article
- Phosphoproteomic profiling of T cell acute lymphoblastic leukemia reveals targetable kinases and combination treatment strategies.Nature communications · 2022Article
- Identification of polo-like kinase 1 as a therapeutic target in murine lupus.Clinical & translational immunology · 2022Article
- Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer.Molecules (Basel, Switzerland) · 2021Review
- Targeting aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia.Scientific reports · 2020Article
- Elevated ABCB1 Expression Confers Acquired Resistance to Aurora Kinase Inhibitor GSK-1070916 in Cancer Cells.Frontiers in pharmacology · 2020Article
- The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?Journal of hematology & oncology · 2019Review
- In vitro study of the Polo-like kinase 1 inhibitor volasertib in non-small-cell lung cancer reveals a role for the tumor suppressor p53.Molecular oncology · 2019Article
- Polo-like kinases and acute leukemia.Oncogene · 2019Review
- Expression and prognostic value of cell-cycle-associated genes in gastric adenocarcinoma.BMC gastroenterology · 2018Article
- The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells.Oncotarget · 2018Article
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- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits cancer cell proliferation.Oncotarget · 2016Article
- Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia.Oncotarget · 2016Article
- A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.Investigational new drugs · 2016Article
- Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polo-like kinases (PLKs) and Aurora kinases (AKs) act as key cell cycle regulators in healthy human cells. In cancer, these protein kinases are often overexpressed and dysregulated, thus contributing to uncontrolled cell proliferation and growth. T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy arising in the thymus from T-cell progenitors. Primary chemoresistant and relapsed T-ALL patients have yet a poor outcome, therefore novel therapies, targeting signaling pathways important for leukemic cell proliferation, are required. Here, we demonstrate the potential therapeutic effects of BI6727, MK-5108, and GSK1070916, three selective inhibitors of PLK1, AK-A, and AK-B/C, respectively, in a panel of T-ALL cell lines and primary cells from T-ALL patients. The drugs were both cytostatic and cytotoxic to T-ALL cells by inducing G2/M-phase arrest and apoptosis. The drugs retained part of their pro-apoptotic activity in the presence of MS-5 bone marrow stromal cells. Moreover, we document for the first time that BI6727 perturbed both the PI3K/Akt/mTORC2 and the MEK/ERK/mTORC1 signaling pathways, and that a combination of BI6727 with specific inhibitors of the aforementioned pathways (MK-2206, CCI-779) displayed significantly synergistic cytotoxic effects. Taken together, our findings indicate that PLK1 and AK inhibitors display the potential for being employed in innovative therapeutic strategies for improving T-ALL patient outcome.
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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.