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Exploring c-Met and HER3 crosstalk by nano-proximity imaging for understanding its clinical significance in lung adenocarcinoma.

Richard Lee

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Medical Research Council (MRC)
The study aims to explore the interaction between two receptors, c-Met and HER3 in lung cancer, in order to understand their role in the development of EGFR-tyrosine kinase inhibitor resistant adenocarcinoma. This will be achieved by using a lung cancer cell model developed in the sponsoring laboratory. This model represents common clinical phenotypes of EGFR (TKI Resistant/sensitive and wildtype). We will image the interaction between c-Met and HER3 in vitro, using this cell model, under basal conditions or with c-Met inhibition. The sponsoring laboratory has proof-of-principle data demonstrating quantification of hetero-dimerisation/oligomerisation of HER family receptors using Förster (Fluorescence) resonance energy transfer (FRET). In addition we will use these cells to develop xenograft tumours in mice, to compare c-Met inhibitor exposed or naive animals. These groups will be assessed for tumour cell proliferation and other tumoral properties, and very importantly, to explore how the c-Met and HER3 interaction is modulated in vivo. The study will finally use archival NSCLC adenocarcinoma sub-type patient specimens (resected primary tumours and regional lymph nodes) to explore the putative interaction between c-Met and HER3 in metastasis and its potential role as a clinical tool in the context of a prognostic model that could predict responsiveness to c-Met inhibitors.

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