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Repurposed drug targeting of metabolic flexibility in cancer / EMMA STANTON

Swansea University Author: EMMA STANTON

  • E-Thesis – open access under embargo until: 21st August 2027

DOI (Published version): 10.23889/SUthesis.70752

Abstract

T-cell acute lymphoblastic leukaemia (T-ALL) and ovarian cancer represent two challenging malignancies with limited treatment options and high relapse rates. T-ALL, comprising 12-15% of acute lymphoblastic leukaemia (ALL) cases in children and 25% in adults, is known for its aggressive nature and po...

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Published: Swansea 2025
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Cronin, James ; Jones, Nick ; Thornton, Cathy
URI: https://cronfa.swan.ac.uk/Record/cronfa70752
first_indexed 2025-10-22T16:02:15Z
last_indexed 2025-10-24T18:48:36Z
id cronfa70752
recordtype RisThesis
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spelling 2025-10-23T11:09:12.1014721 v2 70752 2025-10-22 Repurposed drug targeting of metabolic flexibility in cancer e89b7c2173992c85f256b3449d556b97 EMMA STANTON EMMA STANTON true false 2025-10-22 T-cell acute lymphoblastic leukaemia (T-ALL) and ovarian cancer represent two challenging malignancies with limited treatment options and high relapse rates. T-ALL, comprising 12-15% of acute lymphoblastic leukaemia (ALL) cases in children and 25% in adults, is known for its aggressive nature and poor prognosis following relapse. Despite advances in treating ALL, relapse rates remain high, and survival beyond five years is less than 7%. Current treatments often lead to severe side effects, including graft-vs-host disease and cytokine release syndrome, underscoring the urgent need for more effective and less toxic therapies. Ovarian cancer, predominantly epithelial in origin, also poses significant challenges, with a five-year survival rate of 30%. Resistance to platinum-based chemotherapy affects approximately 80% of patients, highlighting the need for novel therapeutic strategies. This research investigates the potential of repurposed drugs, particularly diclofenac, in treating these malignancies. Diclofenac demonstrated significant anti-cancer activity in both T-ALL and ovarian cancer models. In T-ALL, diclofenac alone induced cell cycle arrest, apoptosis, and increased oxidative stress, while combining diclofenac with asparaginase showed synergistic effects, enhancing cell death and reducing proliferation. However, diclofenac combined with metformin resulted in a rescue effect, suggesting complex interactions that require further exploration. In ovarian cancer, diclofenac, both alone and in combination with metformin and disulfiram, reduced cell viability effectively. These findings indicate that diclofenac and its combinations hold promise for improving cancer treatment efficacy and reducing reliance on conventional therapies. Future research should focus on elucidating the precise mechanisms of these drug interactions, exploring their effects across different cancer genotypes, and comparing their efficacy with current treatments. This approach could lead to more targeted, effective therapies with reduced toxicity, offering hope for better outcomes in patients with T-ALL and ovarian cancer. E-Thesis Swansea 21 8 2025 2025-08-21 10.23889/SUthesis.70752 COLLEGE NANME COLLEGE CODE Swansea University Cronin, James ; Jones, Nick ; Thornton, Cathy Doctoral Ph.D Health Care and Research Wales (HCRW) Not Required Health Care and Research Wales (HCRW) 2025-10-23T11:09:12.1014721 2025-10-22T15:05:55.9264974 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science EMMA STANTON 1 Under embargo Under embargo 2025-10-22T15:28:59.1929724 Output 14370279 application/pdf E-Thesis – open access true 2027-08-21T00:00:00.0000000 Copyright: The Author, Emma Stanton, 2025. true eng
title Repurposed drug targeting of metabolic flexibility in cancer
spellingShingle Repurposed drug targeting of metabolic flexibility in cancer
EMMA STANTON
title_short Repurposed drug targeting of metabolic flexibility in cancer
title_full Repurposed drug targeting of metabolic flexibility in cancer
title_fullStr Repurposed drug targeting of metabolic flexibility in cancer
title_full_unstemmed Repurposed drug targeting of metabolic flexibility in cancer
title_sort Repurposed drug targeting of metabolic flexibility in cancer
author_id_str_mv e89b7c2173992c85f256b3449d556b97
author_id_fullname_str_mv e89b7c2173992c85f256b3449d556b97_***_EMMA STANTON
author EMMA STANTON
author2 EMMA STANTON
format E-Thesis
publishDate 2025
institution Swansea University
doi_str_mv 10.23889/SUthesis.70752
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 0
active_str 0
description T-cell acute lymphoblastic leukaemia (T-ALL) and ovarian cancer represent two challenging malignancies with limited treatment options and high relapse rates. T-ALL, comprising 12-15% of acute lymphoblastic leukaemia (ALL) cases in children and 25% in adults, is known for its aggressive nature and poor prognosis following relapse. Despite advances in treating ALL, relapse rates remain high, and survival beyond five years is less than 7%. Current treatments often lead to severe side effects, including graft-vs-host disease and cytokine release syndrome, underscoring the urgent need for more effective and less toxic therapies. Ovarian cancer, predominantly epithelial in origin, also poses significant challenges, with a five-year survival rate of 30%. Resistance to platinum-based chemotherapy affects approximately 80% of patients, highlighting the need for novel therapeutic strategies. This research investigates the potential of repurposed drugs, particularly diclofenac, in treating these malignancies. Diclofenac demonstrated significant anti-cancer activity in both T-ALL and ovarian cancer models. In T-ALL, diclofenac alone induced cell cycle arrest, apoptosis, and increased oxidative stress, while combining diclofenac with asparaginase showed synergistic effects, enhancing cell death and reducing proliferation. However, diclofenac combined with metformin resulted in a rescue effect, suggesting complex interactions that require further exploration. In ovarian cancer, diclofenac, both alone and in combination with metformin and disulfiram, reduced cell viability effectively. These findings indicate that diclofenac and its combinations hold promise for improving cancer treatment efficacy and reducing reliance on conventional therapies. Future research should focus on elucidating the precise mechanisms of these drug interactions, exploring their effects across different cancer genotypes, and comparing their efficacy with current treatments. This approach could lead to more targeted, effective therapies with reduced toxicity, offering hope for better outcomes in patients with T-ALL and ovarian cancer.
published_date 2025-08-21T05:31:36Z
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score 11.089386

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