MRes - Personalisation of Prostate Cancer Treatment

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Summary

Prostate cancer is the second leading cause of cancer-related death in men globally, with significant heterogeneity in clinical presentation, disease progression, and therapeutic response. While localised prostate cancer can often be managed successfully with surgery or radiotherapy, advanced and metastatic forms present a major treatment challenge. Androgen deprivation therapy (ADT) remains the cornerstone of treatment for advanced prostate cancer; however, many patients eventually progress to castration-resistant prostate cancer (CRPC), which is associated with poor prognosis and limited treatment options [1].

Emerging research has highlighted the biological and molecular diversity of prostate cancer, ranging from androgen receptor (AR)-driven adenocarcinomas to AR-independent neuroendocrine subtypes. This heterogeneity arises from a complex interplay of genetic alterations, such as PTEN loss, TP53 mutations, and gene fusions like TMPRSS2-ERG, which not only drive disease progression but also influence treatment response [2]. As such, a "one-size-fits-all" approach is increasingly inadequate, and there is a pressing need for strategies that personalise therapy based on individual tumour characteristics.

Recent advances in molecular profiling and next-generation sequencing have enabled the identification of prognostic and predictive biomarkers, which can stratify patients and inform therapeutic decisions [3]. Furthermore, developments in in vitro modelling, particularly the use of patient-derived cell lines, 3D spheroids, and organoids, have created powerful platforms for studying tumour biology and testing drug efficacy in a personalised context [4].

By using panels of genetically diverse prostate cancer cell lines, researchers can mimic the molecular spectrum seen in patients and assess differential responses to treatment. Combining these in vitro models with drug sensitivity assays and molecular readouts offers a valuable approach to uncover mechanisms of resistance and guide biomarker discovery. Importantly, 3D models better recapitulate the tumour microenvironment and architecture compared to conventional 2D cultures, potentially offering greater translational relevance [5].

This project aims to investigate how different prostate cancer cell lines with distinct molecular characteristics respond to a panel of standard and experimental treatments. The findings could contribute to developing predictive biomarkers and support the clinical translation of personalised therapeutic approaches.

Objectives of the research:

  1. To characterise the molecular profiles (e.g., AR status, PTEN loss, TMPRSS2-ERG fusion) of selected prostate cancer cell lines.
  1. To assess the differential drug response of these cell lines to various therapeutic agents, including ADT, chemotherapy, and targeted inhibitors.
  1. To identify potential biomarkers predictive of treatment response or resistance.
  1. To evaluate whether 3D culture models offer improved predictive value compared to 2D monolayers

Methods to be used:

Cell Culture: Maintenance of prostate cancer cell lines in both 2D and 3D systems (e.g., spheroids/organoids).

Drug Screening: Treatment with a panel of conventional and experimental agents; measurement of cell viability and apoptosis.

Molecular Profiling: Western blotting, qPCR, and immunofluorescence for key signalling pathways and genetic alterations.

Data Analysis: Statistical comparison of drug responses across models and correlation with molecular features.

Skills required of applicant:

  • Basic cell culture techniques (sterile technique, media preparation, passaging).
  • Familiarity with molecular biology assays (PCR, Western blotting, etc.).
  • An understanding of cancer biology and molecular oncology.
  • Data analysis and interpretation skills (e.g., use of GraphPad, Excel, or R).
  • Ability to work independently and collaboratively in a laboratory environment.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

  • Experience using research methods or other approaches relevant to the subject domain
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement
  • Clearly defined research proposal detailing background, research questions, aims and methodology

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • Work experience relevant to the proposed project

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility

This opportunity is open to UK/ROI applicants only.

MRes studentships will be available to top ranked candidates to cover tuition fees and a Research Training Support Grant of £900. All applicants will be considered automatically for an MRes studentship. Applicants who do not receive a studentship but meet admission requirements may be offered admission on a self-funded basis.

Applicants who already hold an MRes or a doctoral degree or who have been registered on a programme of research leading to the award of an MRes or doctoral degree are NOT eligible to apply for an award. Applicants who hold or who are registered on a taught Master’s degree are eligible to apply.

Recommended reading

Kirby, M., Hirst, C., & Crawford, E. D. (2011). Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice, 65(11), 1180-1192. https://doi.org/10.1111/j.1742-1241.2011.02799.x

Barbieri, C. E., Bangma, C. H., Bjartell, A., et al. (2013). The mutational landscape of prostate cancer. European Urology, 64(4), 567–576. https://doi.org/10.1016/j.eururo.2013.03.032

Armenia, J., Wankowicz, S. A., Liu, D., et al. (2018). The long tail of oncogenic drivers in prostate cancer. Nature Genetics, 50(5), 645–651. https://doi.org/10.1038/s41588-018-0078-z

Gao, D., Vela, I., Sboner, A., et al. (2014). Organoid cultures derived from patients with advanced prostate cancer. Cell, 159(1), 176–187. https://doi.org/10.1016/j.cell.2014.08.016

Puca, L., Bareja, R., Prandi, D., et al. (2018). Patient derived organoids to model rare prostate cancer phenotypes. Nature Communications, 9, 2404. https://doi.org/10.1038/s41467-018-04724-5

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 16 June 2025
04:00PM

Interview Date
End of June / Start of July

Preferred student start date
15/09/2025

Applying

Apply Online  

Contact supervisor

Professor Chris McConville

Other supervisors