Understanding how triple-negative breast cancer cells respond to chemotherapy

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dc.contributor.authorArunasalam, Viboushann
dc.contributor.examiningcommitteeKlonisch, Thomas (Human Anatomy and Cell Science)
dc.contributor.examiningcommitteeKung, Sam (Immunology)
dc.contributor.supervisorLogue , Susan
dc.date.accessioned2024-04-02T19:45:34Z
dc.date.available2024-04-02T19:45:34Z
dc.date.issued2024-03-27
dc.date.submitted2024-03-27T07:31:49Zen_US
dc.degree.disciplineHuman Anatomy and Cell Science
dc.degree.levelMaster of Science (M.Sc.)
dc.description.abstractEvery year over 5,000 Canadians are diagnosed with Triple-Negative Breast Cancer (TNBC), an aggressive subtype of breast cancer with limited treatment options and a poor patient prognosis. The main treatment for TNBC is neoadjuvant chemotherapy followed by tumour resection, and while this can be effective for many patients, there remains a significant number of individuals that experience tumour relapse within 3-5 years post-treatment. Understanding the reason behind frequent relapse is vital in designing novel and effective therapeutic strategies. To this end, we must first elucidate how TNBC cells are responding to standard-of-care chemotherapeutic treatment to better understand the changes that lead to tumour relapse. The objective of my study is to analyze how TNBC cells respond to a clinically-relevant dosage of the commonly used chemotherapeutic, paclitaxel. To achieve this, we used the TNBC cell line, MDA-MB-231, to assess transcriptomic, proteomic, secretomic, and functional changes in response to a clinically-relevant low dosage of the chemotherapeutic paclitaxel. We discovered several gene expression changes in paclitaxel-treated cells that are seen in pro-tumourigenic processes including cancer stem cell expansion, epithelial-mesenchymal transition (EMT), metastasis, and inflammatory signaling. Functional assays of paclitaxel-treated MDA-MB-231 cells confirmed alterations to functional characteristics consistent with the upregulation of genes involved in stemness and inflammatory signaling. However, despite pro-EMT gene expression changes, paclitaxel-treated cells displayed a reduction in migration. These findings propose that MDA-MB-231 cells treated with low-dose paclitaxel undergo alterations in gene expression linked to processes that may support tumour relapse.
dc.description.noteMay 2024
dc.identifier.urihttp://hdl.handle.net/1993/38137
dc.language.isoeng
dc.rightsopen accessen_US
dc.subjectbreast cancer
dc.subjectpaclitaxel
dc.subjectchemotherapy
dc.subjecttranscriptomics
dc.subjectlive-cell imaging
dc.titleUnderstanding how triple-negative breast cancer cells respond to chemotherapy
dc.typemaster thesisen_US
local.subject.manitobano
oaire.awardTitleResearch Manitoba Master's Studentship Award
oaire.awardURIhttps://researchmanitoba.ca/funding/programs/masters-studentship-award/
project.funder.identifierhttps://doi.org/10.13039/100008794
project.funder.nameResearch Manitoba
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