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Stochastic modelling of tyrosine kinase inhibitor rotation therapy in chronic myeloid leukaemia
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. (CCBG;Linnaeus Ctr Biomat Chem, BMC)
Norwegian University of Science and Technology, Norway.
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. (CCBG;Linnaeus Ctr Biomat Chem, BMC)ORCID iD: 0000-0001-8696-3104
2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, p. 1-13, article id 508Article in journal (Refereed) Published
Abstract [en]

BackgroundResistance towards targeted cancer treatments caused by single nucleotide variations is a major issue in many malignancies. Currently, there are a number of available drugs for chronic myeloid leukaemia (CML), which are overcome by different sets of mutations. The main aim of this study was to explore if it can be possible to exploit this and create a treatment protocol that outperforms each drug on its own.MethodsWe present a computer program to test different treatment protocols against CML, based on available resistance mutation growth data. The evolution of a relatively stable pool of cancer stem cells is modelled as a stochastic process, with the growth of cells expressing a tumourigenic protein (here, Abl1) and any emerging mutants determined principally by the drugs used in the therapy.ResultsThere can be some benefit to Bosutinib-Ponatinib rotation therapy even if the mutation status is unknown, whereas Imatinib-Nilotinib rotation is unlikely to improve the outcomes. Furthermore, an interplay between growth inhibition and selection effects generates a non-linear relationship between drug doses and the risk of developing resistance.ConclusionsDrug rotation therapy might be able to delay the onset of resistance in CML patients without costly ongoing observation of mutation status. Moreover, the simulations give credence to the suggestion that lower drug concentrations may achieve better results following major molecular response in CML.

Place, publisher, year, edition, pages
BioMed Central, 2019. Vol. 19, p. 1-13, article id 508
National Category
Bioinformatics and Systems Biology Cancer and Oncology
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-84416DOI: 10.1186/s12885-019-5690-5ISI: 000469322800004PubMedID: 31138173Scopus ID: 2-s2.0-85066397867OAI: oai:DiVA.org:lnu-84416DiVA, id: diva2:1318911
Funder
Swedish Cancer Society, CAN 2015/387Available from: 2019-05-29 Created: 2019-05-29 Last updated: 2019-08-29Bibliographically approved

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Lindström, JonathanFriedman, Ran

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