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TRANS-CASPS: Translational studies in Cedrianib in Alveolar Soft Part Sarcoma (CASPS) trial.

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  • Full or part time
    Dr C Jones
    Dr P Huang
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes. We are committed to attracting and developing the best minds in the world to join us in our mission—to make the discoveries that defeat cancer.

TRANS-CASPS: Translational studies in Cedrianib in Alveolar Soft Part Sarcoma (CASPS) trial.

Project Description:
Alveolar soft part sarcoma (ASPS) is a rare form of sarcoma with poor long-term outlook. Cediranib is a multi-target tyrosine kinase inhibitor (TKI) that exhibits selectivity for a spectrum of receptor tyrosine kinases (RTKs). It has been clinically evaluated for the treatment of selected soft tissue sarcoma (STS) histological subtypes, including alveolar soft part sarcoma (ASPS). In addition to inhibiting VEGFR-mediated angiogenesis, direct inhibition of tyrosine kinase signalling in tumour cells is likely to also contribute to its clinical efficacy. The CASPS trial is a double blind, placebo-controlled randomised trial of the anti-angiogenic agent cediranib in ASPS. A proportion of patients showed a clinical response to this drug but the mechanisms of drug action are unclear. In addition, there are patients who display intrinsic resistance to this drug while those who do respond eventually develop acquired resistance.

There are several important questions that remain to be answered which will be the focus of this studentship: 1. What are the molecular targets of this drug in ASPS? 2. What are the mechanisms of drug resistance and can we identify therapies that could overcome or prevent such resistance from developing and 3. What are the biomarkers of response and resistance to cediranib and can we develop strategies for early detection of drug response?

The project seeks to address these questions by experimentally defining the molecular mechanisms of cediranib response and resistance in ASPS. The overarching objective is to undertake translational studies that employ molecular profiling to characterise tissue and blood specimens collected in the CASPS trial. By assessing the baseline and dynamic molecular alterations associated with therapy response, this approach will define targets of drug action and lead to the characterisation of candidate mechanisms that drive cediranib resistance in ASPS. It is anticipated that this research will accelerate the discovery salvage or combination therapies to achieve durable treatment responses and ultimately improve ASPS patient outcomes.

The project is composed of 3 aims. Aim 1: Define candidate molecular mechanisms of cediranib resistance and sensitivity in ASPS using state-of-the-art molecular profiling approaches (RNAseq, methylation analysis and proteomic profiling by mass spectrometry). Aim 2: Develop liquid biopsies for monitoring cediranib response and disease relapse using serial blood samples from the CASPS trial, including circulating endothelial cell profiling and cytokine analysis. Aim 3: Characterise the tumour microenvironment (immune, inflammatory and matrisome) in ASPS specimens from the CASPS trial using immunohistochemistry, RNASeq and proteomic analysis.

Training and development
The PhD student will be supervised by Dr Robin Jones, Head of the Sarcoma Unit at the Royal Marsden and will benefit from mentorship and training from multi-disciplinary team in Dr Paul Huang’s laboratory within the Division of Molecular Pathology. There will be a close collaboration with the Chief Investigator of the CASPS trial Prof Ian Judson and other research teams at the ICR (Prof. Nick Turner, Dr. Rachael Natrajan and Dr. Yinyin Yuan). The student will be trained in state-of-the-art Omic profiling strategies as well as the latest liquid biopsy analysis techniques. The student will be exposed to Translational research, Sarcoma Molecular Pathology, Cancer Biology, Signal Transduction and Systems Pharmacology.

Funding Notes

Students receive an annual stipend, currently £21,000 per annum, as well as having tuition fees (both UK/EU and overseas) and project costs paid for the four-year duration. We are open to applications from any eligible candidates and are committed to attracting and developing the best minds in the world.
See to apply
Applications close 11:55pm UK time on Sunday 17th November 2019

Candidates must have a first class or upper second class honours BSc Honours/MSc in Biology, Biochemistry, Cancer Biology or a related discipline.

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