Understanding how triple-negative breast cancer cells respond to chemotherapy
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Date
2024-03-27
Authors
Arunasalam, Viboushann
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Abstract
Every 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.
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Keywords
breast cancer, paclitaxel, chemotherapy, transcriptomics, live-cell imaging