Earnshaw, Connor (2024) Investigating the effects of Apaziquone (EO9) in solid tumour Cancer Treatment: A focus on NAD(P)H:quinone oxidoreductase (NQO1) expression in Skin, Nasopharyngeal and Cervical cancers. Masters thesis, York St John University.

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Text (MSc by Research thesis) Investigating the effects of Apaziquone (EO9) in solid tumour Cancer Treatment A focus on NAD(P)Hquinone oxidoreductase (NQO1) expression in Skin, Nasopharyngeal and Cervical cancers. .pdf - Published Version Available under License Creative Commons Attribution. Download (990kB) | Preview

Abstract

Solid tumour cancers pose a significant issue within the research and medical field due to the increase in resistance to conventional treatment options that are often attributed to the presence of hypoxia found within tumour microenvironments. This study investigates the therapeutic potential of EO9 (Apaziquone), a bio reductive alkylating agent previously explored for the treatment of NMIBC, focusing on its activation by the enzyme NAD(P)H:quinone 1 (NQO1). Prior research has established a link between NQO1 activity and EO9 cytotoxicity, this study builds on the idea by looking at the correlation between NQO1 activity levels and EO9’s half-maximal lethal dose (LD50) across cervical, nasopharyngeal and melanoma solid tumour cancer cell lines. Additionally, the research explores the use of catalase inhibitors to enhance the therapeutic efficacy, potentially lowering the drug concentration required for an effective dose. These findings highlight a conjunctive approach that could improve the clinical outcome of EO9, specifically in tumours that express both elevated levels of NQO1 and catalase activity. The results show that EO9 exhibits a lower LD50 in tumour cells with higher NQO1 expression, supporting the idea of the enzyme's role in EO9's bioactivation and selective cytotoxicity. The combined use of catalase inhibitors with EO9 was shown to further reduce the lethal dose of EO9 required for similar therapeutic
effect, suggesting that inhibiting catalase can increase the killing efficacy of EO9, potentially minimizing its
off-target effects and improving patient outcomes. The in vitro findings outlined in this study suggest EO9 has
potential therapeutic effect in Cervical, Nasopharyngeal and Melanoma cancers and may also exhibit greater therapeutic effect when used in conjunction with catalase inhibitors such as 3-AT, Cannaflavin A, ECG+ and myricetin. This data supports the need for further investigation into whether similar therapeutic effects would be seen in other sarcoma, carcinoma, and lymphoma cancers. In conclusion, this study provides compelling evidence for the potential of EO9, particularly in combination with catalase inhibitors, as a new therapeutic approach for solid tumour cancers. This innovative strategy could lead to more effective and less toxic treatments, offering hope for improved patient outcomes.

Item Type:	Thesis (Masters)
Status:	Published
Subjects:	Q Science > Q Science (General)
School/Department:	School of Science, Technology and Health
URI:	https://ray.yorksj.ac.uk/id/eprint/12443

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