Zhou, Chumin
(2023)
Investigating Radiosensitivity of HPV-positive and HPV-negative Head and Neck Squamous Cell Carcinoma Spheroids by PARP Inhibition.
PhD thesis, Unspecified.
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Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most-common cancer over the world, and it remains a significant public health concern in the UK. A number of studies have indicated HPV type-16 infection is one of the main risk factors related with nearly 50% HNSCC cases. Interestingly, the survival rate of HPV-positive HNSCC patients is shown to be higher than HPV-negative status, due to an improved prognosis and better response to chemo- and/or radiotherapeutic strategies. Previously published studies in our group have demonstrated the increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and the efficiency of DNA double strand break (DSB) repair. Therefore in this project, I demonstrate that HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) spheroids show higher radiosensitivity compared to HPV-negative OPSCC spheroids, due to the defective efficacy of DNA DSB repair. Subsequently, PARP inhibitors Olaparib and Talazoparib presented significant enhancement of radio-sensitisation on HPV-negative HNSCC spheroids. Moreover, HNSCC spheroid growth was more effectively suppressed by proton beam therapy in combination these PARP inhibitors. This research suggested that the combination of clinical PARPi and proton irradiation can become a potent treatment for HPV-negative HNSCC patients in the future.
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health and Life Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 Aug 2023 14:05 |
| Last Modified: | 17 Aug 2023 14:05 |
| DOI: | 10.17638/03170491 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3170491 |
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