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DC Field | Value | Language |
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dc.contributor.author | Wong, Alex Xing Fah | en |
dc.date.accessioned | 2019-01-19T13:02:06Z | en |
dc.date.accessioned | 2019-12-06T15:09:17Z | - |
dc.date.available | 2019-01-19T13:02:06Z | en |
dc.date.available | 2019-12-06T15:09:17Z | - |
dc.date.issued | 2018 | en |
dc.identifier.citation | Wong, A. X. F. (2018). Elucidating the role of metabolic changes in modulating cell fate following treatment with anti-mitotic drugs. Doctoral thesis, Nanyang Technological University, Singapore. | en |
dc.identifier.uri | https://hdl.handle.net/10356/82972 | - |
dc.description.abstract | Anti-mitotic drugs are the most-commonly utilised class of chemotherapeutic agents that are administered as first-line therapy; however, their clinical success has been impeded by chemoresistance and disease relapse. Better understanding of the cellular pathways underlying this escape from antimitotic drug-induced cell death, known as mitotic slippage, is crucial for development of combinatorial therapies that can enhance existing treatment regimen in patients. Mitotic slippage describes a phenomenon where cells escape mitotic arrest and cell death following treatment with anti-mitotic drugs, and "slip" into interphase without proper chromosome segregation and cytokinesis. One of the cell fates following mitotic slippage is a cell cycle-enforced G1 arrest where cells eventually enter senescence. However, the consequences of mitotic-slippage induced senescence is unclear for anti-mitotic drug therapy. This thesis seeks to address this conundrum. In my study, my observations revealed that multinucleated post-slippage cells undergo senescence and elicit paracrine pro-tumourigenic effects, both in vitro and in vivo. The SASP factors secreted by post-slippage senescence cells promote migration, invasiveness and angiogenesis. My investigation into potential senescence effectors revealed two major metabolic pathways, autophagy and lipid metabolism, that could abrogate the tumour-promoting effects of antimitotic therapies; either by eliminating pro-tumourigenic senescent cells or by suppressing the secretion of the associated pro-tumorigenic factors. Understanding cell fate post-slippage provides opportunities for the development of novel therapeutic strategies to circumvent antimitotic drug resistance and enhance the treatment efficacy for cancer patients. | en |
dc.format.extent | 122 p. | en |
dc.language.iso | en | en |
dc.subject | DRNTU::Science::Biological sciences::Molecular biology | en |
dc.title | Elucidating the role of metabolic changes in modulating cell fate following treatment with anti-mitotic drugs | en |
dc.type | Thesis | en |
dc.contributor.supervisor | Karen Crasta | en |
dc.contributor.school | Interdisciplinary Graduate School (IGS) | en |
dc.description.degree | Doctor of Philosophy | en |
dc.identifier.doi | 10.32657/10220/47517 | en |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
Appears in Collections: | IGS Theses |
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File | Description | Size | Format | |
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PhD Thesis - school.pdf | PhD Thesis | 17.13 MB | Adobe PDF | ![]() View/Open |
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