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Review
. 2021 Mar 27;22(7):3474.
doi: 10.3390/ijms22073474.

BRAF Gene and Melanoma: Back to the Future

Margaret Ottaviano  1   2   3 , Emilio Francesco Giunta  4 , Marianna Tortora  3 , Marcello Curvietto  5 , Laura Attademo  2 , Davide Bosso  2 , Cinzia Cardalesi  2 , Mario Rosanova  2 , Pietro De Placido  1 , Erica Pietroluongo  1 , Vittorio Riccio  1 , Brigitta Mucci  1 , Sara Parola  1 , Maria Grazia Vitale  5 , Giovannella Palmieri  3 , Bruno Daniele  2 , Ester Simeone  5 , On Behalf Of Scito Youth
Affiliations
Review

BRAF Gene and Melanoma: Back to the Future

Margaret Ottaviano et al. Int J Mol Sci. .

Abstract

As widely acknowledged, 40-50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS-RAF-MEK-ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.

Keywords: BRAF mutation; immunotherapy; melanoma; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main intracellular pathways and processes involved in melanomagenesis. RTK: receptor tyrosine kinase; PIP2: phosphatidylinositol 4,5-bisphosphate; PIP3: phosphatidylinositol (3,4,5)-trisphosphate.
See this image and copyright information in PMC

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