Strategies for Knockdown of Gene Products That Promote Cancer Growth

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Munn, Alan

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Pountney, Dean

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Date
2017
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Abstract

Cancer is second only to cardiovascular disease in the number of deaths every year and millions of deaths are caused by cancer globally. Current therapies for many cancers are still not sufficient to achieve a long term cure. One of the important hallmarks of cancer is rapid cell division. Another hallmark of cancer is avoidance of senescence. Telomere stabilisation facilitates rapid cell division and is one of various factors that contribute to the avoidance of senescence. Telomeres are tandemly repeated sequences found at the end of eukaryotic chromosomes. Telomerase is an enzyme complex that extends telomeric repeat sequences, protects cells from senescence and has a major role in the acquisition of high proliferative potential by cancer cells. Thus, down-regulation of expression of the catalytic subunit of telomerase may be an effective way to treat cancer. Interventions that target cancer metabolism can also prevent proliferation of cancer cells. Downregulation of expression or complete silencing of expression of those genes which encode products that are essential for cancer metabolism is one of the key future strategies for cancer treatment. In this regard, the products of genes including lactate dehydrogenase A (LDHA), monocarboxylate transporter 1 (MCT1), cluster of differentiation 147 (CD147) and pyruvate kinase isoenzyme 2 (PKM2) are critically required for aerobic glycolysis and are possible targets for cancer therapy. Upregulation of expression of these gene products favours tumour progression. Thus, silencing the expression of these gene products may provide a non-conventional approach for cancer treatment.

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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

Cancer treatment

Rapid cell division

Telomerase

Lactate dehydrogenase A (LDHA

Monocarboxylate transporter 1 (MCT1),

Cluster of differentiation 147 (CD147)

Pyruvate kinase isoenzyme 2 (PKM2)

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