ArticlePloS one2013
Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- PLK1 inhibition-based combination therapies for cancer management.Translational oncology · 2022Review
- The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy.Frontiers in genetics · 2022Review
- The Discovery of Novel BCR-ABL Tyrosine Kinase Inhibitors Using a Pharmacophore Modeling and Virtual Screening Approach.Frontiers in cell and developmental biology · 2021Article
- Immunotherapy for Breast Cancer: First FDA Approved Regimen.Discoveries (Craiova, Romania) · 2019Article
- Dasatinib synergises with irinotecan to suppress hepatocellular carcinoma via inhibiting the protein synthesis of PLK1.British journal of cancer · 2017Article
- Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo.Oncotarget · 2017Article
- Different BCR/Abl protein suppression patterns as a converging trait of chronic myeloid leukemia cell adaptation to energy restriction.Oncotarget · 2016Article
- p38MAPK and Chemotherapy: We Always Need to Hear Both Sides of the Story.Frontiers in cell and developmental biology · 2016Review
- A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death.Scientific reports · 2015Article
- Hsp90 Inhibitors for the Treatment of Chronic Myeloid Leukemia.Leukemia research and treatment · 2015Review
- Haematological complete remission by ponatinib and bortezomib in a patient with relapsed, Ph⁺ pre-B acute lymphoblastic leukaemia.BMJ case reports · 2014Article
- Critical physiological and pathological functions of Forkhead Box O tumor suppressors.Discoveries (Craiova, Romania) · 2013Review
- PLK1 is a binding partner and a negative regulator of FOXO3 tumor suppressor.Discoveries (Craiova, Romania)Article
- New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals.Discoveries (Craiova, Romania)Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Emergence of resistance to Tyrosine-Kinase Inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, in Chronic Myelogenous Leukemia (CML) demands new therapeutic strategies. We and others have previously established bortezomib, a selective proteasome inhibitor, as an important potential treatment in CML. Here we show that the combined regimens of bortezomib with mitotic inhibitors, such as the microtubule-stabilizing agent Paclitaxel and the PLK1 inhibitor BI2536, efficiently kill TKIs-resistant and -sensitive Bcr-Abl-positive leukemic cells. Combined treatment activates caspases 8, 9 and 3, which correlate with caspase-induced PARP cleavage. These effects are associated with a marked increase in activation of the stress-related MAP kinases p38MAPK and JNK. Interestingly, combined treatment induces a marked decrease in the total and phosphorylated Bcr-Abl protein levels, and inhibits signaling pathways downstream of Bcr-Abl: downregulation of STAT3 and STAT5 phosphorylation and/or total levels and a decrease in phosphorylation of the Bcr-Abl-associated proteins CrkL and Lyn. Moreover, we found that other mitotic inhibitors (Vincristine and Docetaxel), in combination with bortezomib, also suppress the Bcr-Abl-induced pro-survival signals and result in caspase 3 activation. These results open novel possibilities for the treatment of Bcr-Abl-positive leukemias, especially in the imatinib, dasatinib and nilotinib-resistant CML cases.
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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 Socratic graph.