E-Thesis 94 views
Repurposed drug targeting of metabolic flexibility in cancer / EMMA STANTON
Swansea University Author: EMMA STANTON
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...
| 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 |
| 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 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. |
|---|---|
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Health Care and Research Wales (HCRW) |