Identifying gene receptors for more effective drug treatment

Dr Nicholas Coupe is a clinical consultant at the Churchill hospital (NHS OUH Foundation Trust), specialising in treating patients with melanoma and lung cancer. After having trained as a medical oncologist  in Australia he carried out his D.Phil studies at Oxford as a CRUK Oxford Centre Clinical Research Training Fellow from 2015-2018.

Despite recent advances in the way melanoma is treated, many patients still succumb to the disease. An earlier clinical trial (AVAST-M) identified that patients with BRAF mutant melanoma (representing about half of all melanoma patients) are particularly sensitive to bevacizumab, a drug that inhibits VEGF, a growth factor that promotes new blood vessel growth. Nick’s work focused on identifying the mechanism through which the BRAF mutation in melanoma causes bevacizumab sensitivity, predominately by ascertaining links between the BRAF mutation and VEGF expression.The broader goals of his work were to identify additional therapeutic targets that could help treat patients with melanoma with a BRAF mutation.

Using bioinformatic approaches to analyse multiple data sets (including patient samples from the AVAST-M trial) he identified a number of genes that are overexpressed in BRAF mutant tumours and that one of theseplays a significant role in the secretion of VEGF. The gene Nick identified encodes a receptor which is of interest as it is a potential drug target. Blocking this receptor may potentially inhibit new blood vessel growth in BRAF mutant melanomas and could therefore one day evolve into a therapeutic strategy for patients with this disease.

 Some of Nick’s collaborators within Oxford are Prof Adrian Harris and Prof Francesca Buffa (Department of Oncology), Dr Ruud van Stiphout (Ludwig Institute for Cancer Research, Nuffield Department of Medicine), and Dr Naveed Akbar (Radcliffe Department of Medicine). Nick has been funded by CRUK.

Find out more about Nick’s work with patients on Imogen Cheese’s blog Melanoma Rollercoaster.

Nick’s CRUK #MyWisdom for Melanoma: “be sunsmart today, reduce your risk of melanoma tomorrow”.

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