Thesis

Development of novel combination therapies for the treatment of pancreatic cancer

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Awarding institution
  • University of Strathclyde
Date of award
  • 2024
Thesis identifier
  • T17139
Person Identifier (Local)
  • 201959534
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • In the UK, pancreatic cancer is the 5th most common cause of cancer related deaths, with an average 5-year survival rate of 7.3% and a 10-year survival rate of only 1%, which has remained unchanged since the 1970s. Currently the only curative treatment for pancreatic cancer is surgical resection, however 80% of patients are ineligible for resection as the majority of cases are diagnosed in the later stages of the disease and are inoperable, leaving chemotherapy as the only treatment option. Gemcitabine was first introduced in 1997 and remains a main staple of therapy for pancreatic cancer patients, whether as a monotherapy or in combination. However, despite its widespread use, gemcitabine resistance remains a widespread problem clinically, owing to both intrinsic and acquired resistance mechanisms present in over 80% of pancreatic cancers. There is, therefore, a significant clinical need for alternative treatment options in pancreatic cancer, and to this end we propose the use of the repurposed fumarate drugs dimethyl fumarate (DMF) and monomethyl fumarate (MMF). Both DMF and MMF were previously used for the treatment of multiple sclerosis but have since shown promise as anticancer agents, as DMF and MMF downregulate NRF2 activity, the major transcription factor responsible for the antioxidant response, which we hypothesise enhances the effect of other chemotherapies and radiotherapy in combination. The aims of this project were therefore to develop novel combination therapies utilising DMF and MMF in combination with chemotherapy and external beam radiotherapy (EXBR), which we hypothesise would show promise in inducing reduction in clonogenicity in pancreatic cancer cell lines.
Advisor / supervisor
  • Boyd, Marie
Resource Type
DOI

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