pathway inhibition in prostate cancer (Fixed Term)
Applications are invited for 4-year PhD studentship based in the Department of Oncology, University of Cambridge and the new AstraZeneca Discovery Centre at Cambridge. The student will be working on a collaborative project jointly supervised by Dr Harveer Dev, Dr Simon Pacey (University Department of Oncology) and Dr Josep Forment (Oncology R&D, AstraZeneca) and will have the opportunity to work across the two sites. The project, entitled DNA damage and androgen pathway inhibition in prostate cancer will explore the interplay between these two pathways, placing you at the intersect of cutting edge biological, translational and clinical research.
Prostate cancer is a leading cause of cancer death in men in the UK. Precision medicine offers an opportunity to broaden the therapeutic landscape. This is exemplified by Poly ADP-ribose polymerase inhibitors (PARPi), which provide clinical benefit across various cancers with homologous recombination repair deficiency (HRD).
Unexpectedly, recent phase 3 trials in prostate cancer (PROPEL and TALAPRO-2), demonstrated a survival benefit regardless of HRD status, when PARPi were combined with standard of care androgen pathway inhibition (API). This suggests additional mechanisms of action beyond the established synthetic lethal relationship between HRD and PARPi.
The principle that DNA damaging agents may synergistically interact with androgen receptor inhibition is well supported by the survival benefit gained by combining radiotherapy with API. Consequently, this supports extending the use of DNA damaging agents like PARPi beyond the 25% of HRD biomarker-positive patients that are currently eligible.
This project aims to identify novel genetic determinants that mediate the synergistic response to DNA damaging agents and API combination in prostate cancer, defining their mechanism of action and validating the clinical relevance of these pathways in non-HRD patients.
Techniques relevant to the project will include, but not limited to: cell culture, including primary cell culture, gene editing using CRISPR-Cas9, cell survival assays, immunoblotting, immunofluorescence, flow cytometry, bulk and single-cell RNA sequencing, ChIP and ATAC sequencing.
We are looking for a highly motivated and enthusiastic individual capable of thinking and working independently. Applicants should have or shortly expect to obtain a minimum of a good upper second-class honors degree from a UK university, or an equivalent standard from an overseas university, in a relevant discipline. These positions are open to UK citizens or overseas students who meet the UK residency requirements (home fees) or are able to augment the funds to cover the extra costs associated with international student fees through scholarships or funding schemes. Full details of the University's entrance requirements and scholarships are specified on the following link: https: // www. postgraduate.study.cam.ac.uk/
Full funding covering Maintenance fees at £21,500 per annum and the University Composition Fee is provided for the studentship, with effect from 1 October 2024.
Closing date: 6 October 2023
Interview date: week commencing 17 October 2023
Please ensure that you upload a CV, academic transcript and statement of interest to the 'Upload' section of the online application. If you upload any additional documents that have not been requested, we will not be able to consider these as part of your application.
The successful candidate will be informed via email. Once they have accepted their offer, they will be required to submit an online application for the PhD in Oncology. Full guidance and information will be provided about how to submit the PhD application and is also available on the University of Cambridge Postgraduate Admissions website.
For informal enquiries, please contact Dr Harveer Dev at [email protected]
Please quote reference RD38218 on your application and in any correspondence about this vacancy.
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.
The University has a responsibility to ensure that all employees are eligible to live and work in the UK.Further information
Department of OncologyReference
25 August 2023Closing date
6 October 2023