Targeting Prostate Cancer drivers through the application of Unstable Protein Targeted Chimeras (UPTACs)

About the Project

In castration-resistant prostate cancer (CRPC), the inherently unstable Androgen Receptor, AR becomes aberrantly reactivated through overexpression, point mutations, or the emergence of constitutively active splice variants (e.g., AR-V7), which contribute to therapeutic resistance. These changes are often accompanied by alterations in additional proteins in signalling networks e.g. cell cycle regulators, further supporting AR function. This project aims to examine and validate novel compounds (UPTACs) that bind the accompanying signalling protein of interest (POI), to AR bringing about degradation of the two targets as a novel therapy for CRPC. Proximity inducing agents such as the UPTACs are leading drug discovery developments and this area of research has been highlighted at the 2026 Annual Meeting of the American Association for Cancer Research, with ground breaking discoveries enabling targeting of previously undruggable targets.

This exciting project places a PhD student at the cutting edge of drug discovery technology within a successful and dynamic multi-disciplinary drug discovery team. Taking compounds developed in the Newcastle chemistry group and bringing them forward within the bioscience team, this studentship provides a unique opportunity for a student to reach further into the chemistry/biology interface that drives and sustains modern academic drug discovery. The supervisory team has a strong track record in drug discovery and development, and the university drug discovery team have successfully produced two cancer drugs, the PARP inhibitor, rucaparib, and the FGFR inhibitor, erdafitinib. Further candidate drugs are undergoing evaluation and this project aims to bring forward another approach to targeting a challenging disease and overcoming resistance in CRPC.

The primary supervisor, Prof Hickson has 25 years cancer drug discovery experience (including biotech and pharmaceutical industry), and has worked on a number of clinical projects including for CRPC (e.g. TRC-253, Branch et al, 2021). Prof Hickson will provide training and supervision of testing of compounds in appropriate models, genetic validation of experiments and use of CRPC from Prof Robson’s work. Dr Cano has supervised over 40 PhD students in her career to date and will provide supervision to the student in the NUCancer Medicinal Chemistry laboratories. Dr Cano leads on a number of collaborative studies within the university, including novel therapeutics for CRPC in collaboration with Prof Robson. Prof Robson, has led several national/international prostate cancer research teams with world leading expertise in AR signalling, including development of CRPC models, which will be available to the student.

This innovative studentship will be offered in a world-leading drug discovery laboratory environment with full support and direction to research and publish the findings of this work on the way to achieving a PhD in drug discovery that will equip the student for the future of small molecule cancer drug discovery.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.