The project will commence in September 2022 and has funding for 3 years. The student will be based primarily at the Barts Cancer Institute, Barts and the London School of Medicine and Dentistry (SMD), Charterhouse Square in the City of London. This PhD studentship is funded by Cancer Research UK.
This exciting project will tackle the problem of improving treatment for cancer patients who need it most and understanding the basic biology behind this.
Most solid cancer related deaths are a result of resistance to therapy and metastasis. There is an urgent need to identifying patients who have a high risk of progression to determining alternative treatment strategies. Cells that constitute tumour blood vessels (BVs), including perivascular, supporting mural cells can control these processes.
We have discovered that loss of mural-cell β3-integrin stimulates intracellular signalling pathways resulting in paracrine signals that enhance primary tumour growth without affecting vascularisation. In human cancers, from different stages of progression, low mural β3-integrin expression is associated not only with an increase in cancer size (Wong and Muñoz-Félix et al., Cell 2020) but also with higher cancer stage, relapse rates and enhanced metastasis. These fundamental findings indicate a new mechanism of cancer growth regulation by mural cell β3-integrin with relevance to cancer progression and metastasis.
The successful applicant will learn a range of molecular, cellular and in vivo techniques in laboratory models and in human cancer in order to exploit the molecular mechanisms regulated by mural β3-integrin that specifically promote treatment resistance and metastasis to provide the best potential targets for therapeutic intervention. This exciting project is embedded in the heart of the Hodivala-Dilke Lab at the Barts Cancer Centre, part of the CRUK-City of London partnership with Kings College London, University College London and the Francis Crick Institute. The PhD will involve a multidisciplinary approach using state of the art techniques via cross institute collaborations.
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