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.
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].
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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