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Development and validation of a radiosensitivity gene expression signature in prostate cancer


   Faculty of Biology, Medicine and Health


About the Project

Prostate cancer (PCa) is diagnosed in 1.4 million men globally each year and causes 375,000 deaths, making PCa the second most common cancer and fifth most common cause of death from cancer in men[1].

50,000 men are diagnosed with PCa annually in the UK, and 20,000 of these will have to decide between surgery and radiotherapy (RT). Both treatments have similar success rates but can have different and significant side effects, with 30% of patients experiencing subsequent biochemical relapse. Treatment decision-making is shared between the patient and physician and is currently based on expected side effects, suitability for surgery/RT and on co-morbidities, rather than on the patient’s tumour genomics.

The response of PCa to RT is influenced by mechanisms including DNA damage repair, hypoxia, apoptosis and immune response[2]. Gene expression signatures have been developed which infer disease prognosis post-RT, such as the Torres-Roca pan-cancer signature[3], but none predict response specifically to RT in PCa.

This project aims to derive and validate a gene expression signature which will identify radiosensitive PCa tumours and so guide patients’ treatment choices based on their individual tumour’s genomics. Whole-transcriptome expression data from ~150 paired pre-treatment and post-RT samples will be used to derive a gene signature predicting radiosensitivity. Data from further cohorts of patients who underwent RT (~500 patients), or radical prostatectomy (~1,700 patients), will be analysed together with clinical outcomes to validate the new signature.

Genomic, transcriptomic and epigenomic data from initial and post-RT samples will be studied to characterise the clonal evolution of PCa tumours treated with RT and to investigate the contributions to post-treatment relapse of intrinsic[4] and acquired[5] radiosensitivity. This project will lead to an improved understanding of why PCa tumours fail to respond to RT, leading to improved outcomes, both specifically for PCa and more generally for other RT-treatable cancers.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website View Website

References

1. De Silva, F. and J. Alcorn, A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer. Cancers (Basel), 2022. 14(12).
2. Silva, P., et al., Clinical and biological factors affecting response to radiotherapy in patients with head and neck cancer: a review. Clin Otolaryngol, 2007. 32(5): p. 337-45.
3. Scott, J.G., et al., A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol, 2017. 18(2): p. 202-211.
4. Arrayeh, E., et al., Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys, 2012. 82(5): p. e787-93.
5. Taghian, A., et al., In vitro intrinsic radiation sensitivity of glioblastoma multiforme. Int J Radiat Oncol Biol Phys, 1992. 23(1): p. 55-62.

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