The Therapeutic Potential of mTOR signalling Pathway as Drug Target in Human Colorectal Cancer
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Wei, Ming
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Hashimi, Saeed
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Abstract
The mammalian target of rapamycin (mTOR), a downstream effector of PI3K/Akt signalling, is a critical regulator of cellular processes in response to oncogenic signals. In mammalian cells, mTOR exists in 2 large physically and functionally distinct signalling complexes, i.e.: mTORC1 and mTORC2. Each complex has its own set of downstream targets, which modulate cellular growth, proliferation, and survival in normal cells and cancer. Deregulation of mTOR signalling often occurs in a variety of human malignant diseases, making it a validated target in the development of treatments for cancer. In colorectal cancer, both in vitro and in vivo studies have demonstrated various roles for different genes, including those related to the mTOR pathway in the pathogenesis of cancer. Clinical trials have already started to examine the feasibility of mTOR inhibitors as therapeutic drugs for cancer. In this study, our objectives were firstly to investigate the expression levels of mTOR in human pathological samples of colorectal cancer and subsequently investigate the effect of mTOR inhibitors in human colorectal cancer cell lines. Finally, the study sought to identify potential miRNAs with putative targets in the mTOR pathway.
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Thesis (PhD Doctorate)
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Doctor of Philosophy (PhD)
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School of Medical Science
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The author owns the copyright in this thesis, unless stated otherwise.
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Subject
Mammalian target of rapamycin (mTOR)
Colorectal Cancer
mTOR inhibitors