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Exploring DNA damage response of prostate cancer and impact of hormone therapy of castration resistant prostate cancer


Project Description

In association with the University of Surrey Doctoral College Dr. Mohammad Asim’s Prostate Cancer Research laboratory is offering a PhD studentship to start from October 2019. This is 3-year, fully-funded post and covers the tuition fee for EU/UK students, offering a tax-free yearly stipend of £15,000.

Prostate cancer (PrCa) is a leading cause of cancer related male mortality in the United Kingdom with over 10,000 deaths each year. The growth and progression of PrCa is regulated by androgens, which manifest their action by activating the androgen receptor (AR), a ligand activated transcription factor that in turn regulates the growth of PrCa. Since AR signaling is upregulated in PrCa, it is an attractive drug target in the treatment of the advanced PrCa.

Hence, widely used androgen deprivation therapy (ADT) is the mainstay treatment for PrCa, which is achieved by the use of anti-androgenic drugs such as Bicalutamide and Enzalutamide. ADT is initially effective but relapse is common leading to castration resistant prostate cancer (CRPC) for which there are no curative treatments.

The key question is why does ADT fail and how does the resistance to ADT emerge? We have recently shown in a study published in Nature Communications that AR regulates DNA damage response (DDR) in CRPC but the molecular determinants that mount the DDR remain unknown. In collaboration with the Nuffield Department of Surgical Sciences, University of Oxford, this project will discover novel determinants of DDR which will eventually pave the way for the development of novel therapeutic strategies for the treatment of CRPC.

Overall, the findings of this study will pave the way to effectively treat CRPC in order to alleviate the disease burden.

Lab website: https://www.surrey.ac.uk/people/mohammad-asim

The research will be done in collaboration with the University of Oxford, where Dr Asim holds honorary scientist posts. The research will involve testing on human cancer tissue specimen available through a collaboration with Prof. Pandha (Royal Surrey County Hospital).

Funding Notes

This studentship is provided by the University of Surrey Doctoral College.

Eligibility: You must have, or expect to achieve, at least a 2:1 honours degree or international equivalent. If English is not your first language, you must have IELTS 7 with at least 6.5 in all the components.

How to apply: Please email to discuss the project and advice on completing the studentship form before applying through the University’s Doctoral College

References

References:

1. Anne Y. Warren, Charlie E. Massie, ---- David E. Neal and Mohammad Asim$ (2018) A reciprocal feedback between the PDZ binding kinase and androgen receptor in prostate cancer. Oncogene 2018 Sep 20. doi: 10.1038/s41388-018-0501-z. [Epub ahead of print]

2. Asim M, Tarish F, ---Neal DE and Helleday T (2017) Synthetic Lethality between androgen signaling and PARP pathway in Prostate Cancer. Nat Commun. Aug 29;8(1):374.

3. Asim M, Massie CE & Neal DE (2016) Kinase Joins the Chaperone Club: Androgen-Regulated Kinome Reveals Choline Kinase Alpha as Potential Drug Target in Prostate Cancer. Molecular & Cellular Oncology Feb 24;3(3):e1140262.

4. Asim M, Massie CE, ---Tilley WD, & Neal DE. (2015) Choline kinase alpha is an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target J Natl Cancer Inst. 2015 Dec 11;108(5).

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