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Title: Analysis of BRAF inhibitor resistance in melanoma cells
Author: Wilkinson, Beth
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2020
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Full text unavailable from EThOS. Thesis embargoed until 01 Jul 2022
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Malignant melanoma is a highly aggressive and metastatic form of skin cancer with more than 2500 skin cancer related deaths in 2014 in the UK alone. This type of melanoma has a high prevalence of BRAF mutations (90% BRAFV600E) which causes an overactive MAPK signalling cascade leading to excessive proliferation, survival and enhanced angiogenic potential. Vemurafenib and dabrafenib are BRAFV600E specific kinase inhibitors which selectively bind the ATP-binding site supressing ERK activity and inhibits its oncogenic activity. All patients become resistant to these BRAFV600E inhibitors at 6-9 months with multiple mechanisms proposed. This thesis explored the activation of ERK5, an atypical MAPK usually involved in normal physiological processes, seen in PLX 4720 and dabrafenib resistant melanoma cells and the potential of this MAPK in driving resistance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral