Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

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

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Palumbo G., Di Lorenzo G., Ottaviano M., Damiano V. The future of melanoma therapy: Developing new drugs and improving the use of old ones. Future Oncol. 2016;12:2531–2534. doi: 10.2217/fon-2015-0045. - DOI - PubMed
    1. Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., Clegg S., Teague J., Woffendin H., Garnett M.J., Bottomley W., et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–954. doi: 10.1038/nature00766. - DOI - PubMed
    1. Funck-Brentano E., Malissen N., Roger A., Lebbé C., Deilhes F., Frénard C., Dréno B., Meyer N., Grob J.J., Tétu P., et al. Which adjuvant treatment for patients with BRAFV600-mutant cutaneous melanoma? In: Cribier B., editor. Annales de Dermatologie et de Vénéréologie. Elsevier; Amsterdam, The Netherlands: 2021. - PubMed
    1. Giunta E.F., De Falco V., Napolitano S., Argenziano G., Brancaccio G., Moscarella E., Ciardiello D., Ciardiello F., Troiani T. Optimal treatment strategy for metastatic melanoma patients harboring BRAF-V600 mutations. Ther. Adv. Med. Oncol. 2020;12:1758835920925219. doi: 10.1177/1758835920925219. - DOI - PMC - PubMed
    1. Ottaviano M., De Placido S., Ascierto P.A. Recent success and limitations of immune checkpoint inhibitors for cancer: A lesson from melanoma. Virchows Arch. 2019;474:421–432. doi: 10.1007/s00428-019-02538-4. - DOI - PubMed

MeSH terms

Substances