ANALYSIS OF BRAFINHIBITOR RESISTANCE IN MELANOMA CELLS



Wilkinson, Beth
(2020) ANALYSIS OF BRAFINHIBITOR RESISTANCE IN MELANOMA CELLS. PhD thesis, University of Liverpool.

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Abstract

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.

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine
Depositing User: Symplectic Admin
Date Deposited: 15 Jan 2021 14:43
Last Modified: 18 Jan 2023 23:23
DOI: 10.17638/03106181
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3106181