ArticleBMC cancer2020
The effects of combination treatments on drug resistance in chronic myeloid leukaemia: an evaluation of the tyrosine kinase inhibitors axitinib and asciminib.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia.International journal of molecular sciences · 2024Pooled it
- Targeting leukemic stem and progenitor cells expressing different BCR::ABL1 levels: antileukemic activity of asciminib with or without TKIs.Frontiers in pharmacology · 2026Article
- Exploring the Allosteric Pathways of Asciminib in the Dual Inhibition of BCR-ABL1.Biomolecules · 2025Article
- A computational dynamic model of combination treatment for type II inhibitors with asciminib.Protein science : a publication of the Protein Society · 2025Article
- Article
- Current and future of targeted therapies against BCR::ABL kinases.Journal of the Egyptian National Cancer Institute · 2025Review
- Discovery ofMolecules (Basel, Switzerland) · 2025Article
- Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia.Blood · 2025Article
- Asciminib and inotuzumab ozogamicin: a new combination for highly refractory Ph-positive B-cell acute lymphoblastic leukemia.Leukemia research reports · 2025Article
- Beyond IC50-A computational dynamic model of drug resistance in enzyme inhibition treatment.PLoS computational biology · 2024Article
- Hallmarks of cancer resistance.iScience · 2024Review
- Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.Biomarker research · 2024Article
- Asciminib in the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia: Focus on Patient Selection and Outcomes.Cancer management and research · 2023Review
- Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire.Protein science : a publication of the Protein Society · 2023Article
- The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia.Biophysical journal · 2022Article
- Novel Naturally Occurring Dipeptides and Single-Stranded Oligonucleotide Act as Entry Inhibitors and Exhibit a Strong Synergistic Anti-HIV-1 Profile.Infectious diseases and therapy · 2022Article
- Rotating between ponatinib and imatinib temporarily increases the efficacy of imatinib as shown in a chronic myeloid leukaemia model.Scientific reports · 2022Article
- Review
- Computational Identification of BCR-ABL Oncogenic Signaling as a Candidate Target of Withaferin A and Withanone.Biomolecules · 2022Article
- Target spectrum of the BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia.International journal of hematology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChronic myeloid leukaemia is in principle a treatable malignancy but drug resistance is lowering survival. Recent drug discoveries have opened up new options for drug combinations, which is a concept used in other areas for preventing drug resistance. Two of these are (I) Axitinib, which inhibits the T315I mutation of BCR-ABL1, a main source of drug resistance, and (II) Asciminib, which has been developed as an allosteric BCR-ABL1 inhibitor, targeting an entirely different binding site, and as such does not compete for binding with other drugs. These drugs offer new treatment options.
methodsWe measured the proliferation of KCL-22 cells exposed to imatinib-dasatinib, imatinib-asciminib and dasatinib-asciminib combinations and calculated combination index graphs for each case. Moreover, using the median-effect equation we calculated how much axitinib can reduce the growth advantage of T315I mutant clones in combination with available drugs. In addition, we calculated how much the total drug burden could be reduced by combinations using asciminib and other drugs, and evaluated which mutations such combinations might be sensitive to.
resultsAsciminib had synergistic interactions with imatinib or dasatinib in KCL-22 cells at high degrees of inhibition. Interestingly, some antagonism between asciminib and the other drugs was present at lower degrees on inhibition. Simulations revealed that asciminib may allow for dose reductions, and its complementary resistance profile could reduce the risk of mutation based resistance. Axitinib, however, had only a minor effect on T315I growth advantage.
conclusionsGiven how asciminib combinations were synergistic in vitro, our modelling suggests that drug combinations involving asciminib should allow for lower total drug doses, and may result in a reduced spectrum of observed resistance mutations. On the other hand, a combination involving axitinib was not shown to be useful in countering drug resistance.
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Registered trials
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