dc.contributor.author | Lindstrom, H Jonathan G | |
dc.contributor.author | de Wijn, Astrid S. | |
dc.contributor.author | Friedman, Ran | |
dc.date.accessioned | 2019-09-30T08:09:08Z | |
dc.date.available | 2019-09-30T08:09:08Z | |
dc.date.created | 2019-07-02T12:41:35Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | BMC Cancer. 2019, 19 (1), 1-13. | nb_NO |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | http://hdl.handle.net/11250/2619288 | |
dc.description.abstract | Background
Resistance 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.
Methods
We 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.
Results
There 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.
Conclusions
Drug 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. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | BioMed Central | nb_NO |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Stochastic modelling of tyrosine kinase inhibitor rotation therapy in chronic myeloid leukaemia | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.pagenumber | 1-13 | nb_NO |
dc.source.volume | 19 | nb_NO |
dc.source.journal | BMC Cancer | nb_NO |
dc.source.issue | 1 | nb_NO |
dc.identifier.doi | 10.1186/s12885-019-5690-5 | |
dc.identifier.cristin | 1709335 | |
dc.description.localcode | Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. | nb_NO |
cristin.unitcode | 194,64,92,0 | |
cristin.unitname | Institutt for maskinteknikk og produksjon | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |