(MCRC Non-Clinical RadNet) Biomarkers of response and toxicity with a novel apoptosis promoting drug in locally advanced cervix cancer at The University of Manchester on FindAPhD.com

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Prof Kaye Williams, Prof Ananya Choudhury, Prof Peter Hoskin No more applications being accepted Competition Funded PhD Project (Students Worldwide)

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Manchester United Kingdom Cancer Biology Immunology Neuroscience Pathology

Faculty of Biology, Medicine and Health, The University of Manchester

About the Project

Cervical cancer affects over 3,000 women a year in the UK. Half of these women are below the age of 45 years. Even with modern treatment, 1 in 3 women will die within 5 years. Current treatment for advanced cervical cancer combines external radiotherapy and chemotherapy (chemoradiation; CRT) followed by internal radiotherapy (brachytherapy).

CRAIN is a CRUK funded phase I/II study of ASTX660 a novel inhibitor of IAPs (Inhibitor of Apoptosis Protein) administered with CRT for locally advanced cervical cancer. Hypoxia underpins treatment resistance for radiotherapy and chemotherapy and can alter the cell death response by decreasing the expression of pro-apoptotic proteins and increasing the expression of anti-apoptotic proteins. Within the CRAIN study, a translational component is included to collect blood and tissue samples to explore the mechanism of interaction between ASTX660 and CRT, focusing on markers of hypoxia and apoptosis.

In addition, we have access to blood and tissue samples from 20 women who have received standard CRT without ASTX660 as part of an ongoing study, BIOCHECC who will provide a control population.

This PhD project will use in silico data, data from the BIOCHECC and CRAIN studies and in vitro techniques to interrogate the biological interplay between CRT, hypoxia and apoptosis in cervix cancer with the aim of identifying profiles which predict response to CRT and the combination of CRT and ASTX660 as measured by post treatment MR scans. Within the CRAIN trial, there is detailed collection of toxicity data and similar predictive profiles will be explored in relation to significant (≥Grade 2) toxic events. We, therefore, hope to identify a biomarker profile based on serum samples which will be used to develop new treatment paradigms and personalise treatment options for women with locally advanced cervical cancer within further biomarker driven phase 2/3 trials.

Kaye Williams

https://www.research.manchester.ac.uk/portal/kaye.williams.html

Entry Requirements

Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage.

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the CRUK Manchester Centre PhD Training Scheme (MCRC) website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/

General enquiries can be directed to [Email Address Removed].

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/

The CRUK RadNet Manchester Unit was one of only three major units awarded. It builds on the 10-year history of an external collaborating “One Manchester” approach to cancer team science in radiotherapy-related research (RRR). This has been achieved by our multi-disciplinary expertise in biology, clinical oncology, physics, software development, engineering and imaging. Manchester is recognised nationally as a Clinical and Translational Radiotherapy Research Working Group (CTRad) Centre of Excellence in Radiotherapy Research and the only centre in the UK with strength across all disciplines (biology, clinical, physics, technology).

The CRUK RadNet Manchester Unit Vision statement is: “As an integrated world-leading translational radiation oncology programme, we address the challenges of diverse patient characteristics to achieve individualised physical and biological targeting based on real-time outcomes and a deep mechanistic understanding of immune response, comorbidity and genomics.” This Vision aligns with CRUK’s research strategy through Collaborative Hubs and new science.

Interview date – WB 4 April 2022

Funding Notes

This project is funded via CRUK RadNet Manchester. Funding will cover UK tuition fees/stipend only (currently at £19,000 per annum) and running expenses. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable a limited number of full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
The duration of this project is four years to commence on 1 October 2022.

References

1. http://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp
2. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. J Clin Oncol. 2008;26(35):5802-12.
3. Lewis S, et al. Br J Radiol. 2018;91(1092):20180005.
4. Mell LK, et al. Int J Radiat Oncol Biol Phys. 2006;66(5):1356-65.
5. Hanahan D & Weinberg RA. Cell. 2011;144(5):646-74.
6. Zhang Y et al. Cell Res. 2018:28(1):9-21
7. Rana NK et al. Biological Research. 2019; 52(1):12
8. Fulda S & Vucic D. Nat Rev Drug Discov. 2012;11(2):109-24.
9. Tilborghs S et al. Crit Rev Oncol Hematol. 2017;120:141-150
10. Saxena K & Jolly MK. Biomolecules .2019; 9:339.