Investigating the radiobiology of protons and BNCT in head and neck tumour treatment


   Institute of Cancer and Genomic Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Background

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide with an annual incidence of ~800,000 cases/year. There has been a particularly rapid rise in the incidence of human papillomavirus type 16 (HPV)-associated tumours of the oropharynx. However interestingly, HPV-positive patients respond better to radiotherapy and chemotherapy in comparison to patients with HPV-negative disease whose outcome is very poor. Despite this, acute and long-term side effects of radiotherapy treatment in HNSCC patients are common. Therefore, more targeted and effective treatments for HNSCC, particularly radioresistant HPV-negative disease, are actively being sought.

Proton beam therapy (PBT) is capable of delivering radiation of a higher biological effectiveness direct to the tumour. Furthermore, the delivery of PBT at ultra-high dose rates (>40 Gy/s; FLASH) has been shown to promote significant normal tissue sparing whilst still maintaining tumour control. Boron neutron capture therapy (BNCT) is an alternative targeted treatment in which specific uptake of boronated compounds by the tumour cells and irradiation with thermal neutron beams generates highly reactive particle ions causing cell death. However, there is significant biological and clinical uncertainty in the utilisation of these novel radiotherapy techniques, although they have huge translational potential for patient benefit.

Objectives

This exciting PhD studentship will develop novel research investigating the comparative effect of PBT at both conventional and FLASH (>40 Gy/s) dose rates and BNCT, in comparison to conventional X-ray radiation, at the molecular and cellular level, using normal and tumour cell models of HNSCC. This will be achieved through the use of established 2D cell lines, 3D spheroids and pair-matched patient-derived organoids. The project will involve an examination of end-points such as cell survival, DNA damage and repair, and cell death mechanisms. The long-term goal of the project is to enhance our biological understanding of PBT at FLASH dose rates, as well as BNCT, particularly using tumour models of HNSCC, and to contribute to determining the optimal radiotherapy treatment and improving overall survival of HNSCC patients.

Impact and training

This molecular and cellular biology-focussed research project will utilise the unique resources present at the University of Birmingham, including the MC40 cyclotron for proton irradiations at both conventional and FLASH dose rates and the high flux accelerator-driven neutron facility for BNCT. This novel work is at the interface of clinical and translational medicine, and which has high translational potential in the establishment of more effective and safer treatments for HNSCC using radiotherapy, particularly PBT and BNCT.

How to apply

Applications should be directed to Professor Jason Parsons at . To apply, please send:

·        A Detailed CV, including your nationality and country of birth;

·        Names and addresses of two referees;

·        A covering letter highlighting your research experience/capabilities;

·        Copies of your degree transcripts;

·        Evidence of your proficiency in the English language, if applicable.

Biological Sciences (4)

Funding Notes

Applications are invited from self-funded students. Candidates are expected to hold (or about to obtain) a minimum second-class honours degree (or equivalent) in a related area/subject.

References

1. Zhou, C., Fabbrizi, M.R., Hughes, J.R., Grundy, G.J., and Parsons, J.L. (2022) Effectiveness of PARP inhibition in enhancing the radiosensitivity of 3D spheroids of head and neck squamous cell carcinoma. Front. Oncol., 12:940377. doi: 10.3389/fonc.2022.940377.
2. Nickson, C.M., Fabbrizi, M.R., Carter, R.J., Hughes, J.R., Kacperek, A., Hill, M.A., and Parsons, J.L. (2021) USP9X is required to maintain cell survival in response to high-LET radiation. Front. Oncol., 11:671431. doi: 10.3389/fonc.2021.671431.
3. Hughes, J.R., and Parsons, J.L. (2020) FLASH radiotherapy: Current knowledge and future insights using proton beam therapy. Int. J. Mol. Sci., 18:6492, doi: 10.3389/ijms21186492.
4. Zhou, C., and Parsons, J.L. (2020) The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma. Expert Rev. Mol. Med., 22:e3, doi: 10.1017/erm.2020.4.
5. Vitti, E-T., Kacperek, A., and Parsons, J.L. (2020) Targeting DNA double-strand break repair enhances radiosensitivity of HPV-positive and HPV-negative head and neck squamous cell carcinoma to photons and protons. Cancers., 12 (6):1490, doi: 10.3390/cancers12061490.
6. Carter, R.J., Nickson, C.M., Thompson, J.M., Kacperek, A., Hill, M.A., and Parsons, J.L. (2019) Characterisation of deubiquitylating enzymes involved in the cellular response to high-LET ionising radiation and complex DNA damage. Int. J. Radiat. Oncol. Biol. Phys., 104 (3), 656-665, doi: 10.1016/j.ijrobp.2019.02.053.
7. Carter, R.J., Nickson, C.M., Thompson, J.M., Kacperek, A., Hill, M.A., and Parsons, J.L. (2018) Complex DNA damage induced by high linear energy transfer alpha-particles and protons triggers a specific cellular DNA damage response. Int. J. Radiat. Oncol. Biol. Phys., 100 (3), 776-784, doi: 10.1016/j.ijrobp.2017.11.012.

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