Abstract

Background

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.

Major conclusions

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.

General significance

The evidence presented suggest that the use of a combinatorial treatment approach would delay the emergence of resistance and improve patient outcomes.

RAS ID

32397

Document Type

Journal Article

Date of Publication

2020

Funding Information

Edith Cowan University - Open Access Support Scheme 2020

School

School of Medical and Health Sciences

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Publisher

Elsevier

Comments

Tangella, L. P., Clark, M. E., & Gray, E. S. (2020). Resistance mechanisms to targeted therapy in BRAF-mutant melanoma-A mini review. Biochimica et Biophysica Acta (BBA)-General Subjects, 1865, Article 129736. https://doi.org/10.1016/j.bbagen.2020.129736

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Link to publisher version (DOI)

10.1016/j.bbagen.2020.129736