Lokeswari P. Tangella
Michael E. Clark
Elin S. Gray
Biochimica et Biophysica Acta
School of Medical and Health Sciences
Edith Cowan University - Open Access Support Scheme
The introduction of targeted therapies for the treatment of BRAF-mutant melanomas have improved survival rates in a significant proportion of patients. Nonetheless, the emergence of resistance to treatment remains inevitable in most patients.
Scope of review
Here, we review known and emerging molecular mechanisms that underlay the development of resistance to MAPK inhibition in melanoma cells and the potential strategies to overcome these mechanisms.
Multiple genetic and non-genetic mechanisms contribute to treatment failure, commonly leading to the reactivation of the MAPK pathway. A variety of resistance mechanisms are enabled by the underlying heterogeneity and plasticity of melanoma cells. Moreover, it has become apparent that resistance to targeted therapy is underpinned by early functional adaptations involving the rewiring of cell states and metabolic pathways.
The evidence presented suggest that the use of a combinatorial treatment approach would delay the emergence of resistance and improve patient outcomes.
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