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Review

Targeting the ERK Signaling Pathway in Melanoma

1
Department of Health Science, University of Eastern Piedmont, via Solaroli 17, 28100 Novara, Italy
2
Section of Dermatology, Department of Medical Science, University of Turin, 10124 Turin, Italy
3
San Raffaele Scientific Institute, Division of Neuroscience, via Olgettina 58, 20132 Milano, Italy
4
Università Vita Salute San Raffaele, via Olgettina 58, 20132 Milano, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1483; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061483
Received: 2 March 2019 / Revised: 17 March 2019 / Accepted: 19 March 2019 / Published: 25 March 2019
(This article belongs to the Special Issue ERK Signaling Pathway in Diseases)
The discovery of the role of the RAS/RAF/MEK/ERK pathway in melanomagenesis and its progression have opened a new era in the treatment of this tumor. Vemurafenib was the first specific kinase inhibitor approved for therapy of advanced melanomas harboring BRAF-activating mutations, followed by dabrafenib and encorafenib. However, despite the excellent results of first-generation kinase inhibitors in terms of response rate, the average duration of the response was short, due to the onset of genetic and epigenetic resistance mechanisms. The combination therapy with MEK inhibitors is an excellent strategy to circumvent drug resistance, with the additional advantage of reducing side effects due to the paradoxical reactivation of the MAPK pathway. The recent development of RAS and extracellular signal-related kinases (ERK) inhibitors promises to add new players for the ultimate suppression of this signaling pathway and the control of pathway-related drug resistance. In this review, we analyze the pharmacological, preclinical, and clinical trial data of the various MAPK pathway inhibitors, with a keen interest for their clinical applicability in the management of advanced melanoma. View Full-Text
Keywords: ERK pathway; target therapy; metastatic melanoma; BRAF inhibitors; MEK inhibitors; ERK inhibitors; NRAS inhibitors; melanoma treatment ERK pathway; target therapy; metastatic melanoma; BRAF inhibitors; MEK inhibitors; ERK inhibitors; NRAS inhibitors; melanoma treatment
MDPI and ACS Style

Savoia, P.; Fava, P.; Casoni, F.; Cremona, O. Targeting the ERK Signaling Pathway in Melanoma. Int. J. Mol. Sci. 2019, 20, 1483. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061483

AMA Style

Savoia P, Fava P, Casoni F, Cremona O. Targeting the ERK Signaling Pathway in Melanoma. International Journal of Molecular Sciences. 2019; 20(6):1483. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061483

Chicago/Turabian Style

Savoia, Paola, Paolo Fava, Filippo Casoni, and Ottavio Cremona. 2019. "Targeting the ERK Signaling Pathway in Melanoma" International Journal of Molecular Sciences 20, no. 6: 1483. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061483

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