Targeting the PI3K and Ras Signal Transduction Pathways in a Murine Model of Osteolytic Breast Cancer Metastasis

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atmire.migration.oldid658
dc.contributor.advisorJirik, Frank
dc.contributor.authorBosma, Nicholas
dc.date.accessioned2013-01-25T17:23:26Z
dc.date.available2015-07-31T07:00:47Z
dc.date.issued2013-01-25
dc.date.submitted2013en
dc.description.abstractBone metastasis frequently occurs in patients with advanced breast cancer, and leads to widespread bone destruction. Aberrant activation of the PI3K and Ras-MAPK pathways are consistently observed in high-grade metastatic breast cancers, making these pathways attractive targets for therapeutic intervention. Complex signal crosstalk between these pathways is implicated in cancer cell perpetuation; therefore, dual inhibition should theoretically provide maximal targeting. The PI3K and MEK inhibitors, PX866 and AZD6244 were employed to investigate the therapeutic potential in an in vivo model of MDA-MB-231-EGFP/Luc2 human breast cancer osteolytic metastases. PI3K inhibition did not directly affect bone-colonized cancer cells, however, it demonstrated an attenuation of bone loss, whereas MEK inhibition resulted in a significant reduction of both tumor growth and osteolysis. Simultaneous inhibition of PI3K and MEK resulted in a reduction of tumor growth, but paradoxically exhibited an exacerbation of bone damage. These findings suggest that MEK inhibition alone may be a valuable additional treatment for breast cancer osteolytic metastasis.en_US
dc.description.embargotermsindefiniteen_US
dc.identifier.citationBosma, N. (2013). Targeting the PI3K and Ras Signal Transduction Pathways in a Murine Model of Osteolytic Breast Cancer Metastasis (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27979en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27979
dc.identifier.urihttp://hdl.handle.net/11023/474
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.facultyMedicine
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology--Molecular
dc.subjectOncology
dc.subjectBiochemistry
dc.subjectBiology--Molecular
dc.subject.classificationPre-clinicalen_US
dc.subject.classificationExperimentalen_US
dc.subject.classificationOncologyen_US
dc.titleTargeting the PI3K and Ras Signal Transduction Pathways in a Murine Model of Osteolytic Breast Cancer Metastasis
dc.typemaster thesis
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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