- Title
- Examining the expression of nucleotide excision repair genes in melanoma tumours
- Creator
- Davey, Ryan James
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2017
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Melanoma is an aggressive form of cancer characterised by poor prognosis and resistance to treatment. Despite recent advances in melanoma treatment, patient outcomes continue to be underwhelming. After these new therapies showed initial promise; resistance and poor duration of response have limited their effectiveness as monotherapies. We are currently at the forefront of a wave of research into the underlying mechanisms of melanoma characteristics. It is now understood that for effective treatments to be developed, we must have a greater understanding of the genetic mechanisms of melanoma’s treatment resistance and abnormally aggressive phenotype. Ultraviolet radiation (UVR) has continually been intrinsically linked to melanoma development. In addition to this, resistance to traditional DNA-damaging chemotherapy drugs such as cisplatin remains a hallmark of melanoma cells. Nucleotide excision repair (NER) orchestrates the repair of helix distorting DNA damage, induced by both ultraviolet radiation (UVR) and cisplatin. There is evidence that the global genome repair (GGR) arm of NER is dysfunctional in melanoma and it is known to have limited induction in melanoma cell lines after cisplatin treatment. To further investigate the links between NER and melanoma, we examined the expression of multiple key genes involved in the NER pathway function and regulation, in a cohort of melanoma tumours. The expression of these transcripts was then compared to clinical parameters. In addition to this, expression of GGR damage recognition protein, XPC, was also quantified in melanoma tumours.
- Subject
- melanoma; treatment; targeted therapy; immunotherapy; combination therapy
- Identifier
- http://hdl.handle.net/1959.13/1337722
- Identifier
- uon:27892
- Rights
- Copyright 2017 Ryan James Davey
- Language
- eng
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| Thumbnail | File | Description | Size | Format | |||
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| View Details Download | ATTACHMENT01 | Thesis | 6 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 156 KB | Adobe Acrobat PDF | View Details Download |