Skip to main content
Top
Published in: Journal of Translational Medicine 1/2010

Open Access 01-12-2010 | Commentary

Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032

Authors: Jill C Rubinstein, Mario Sznol, Anna C Pavlick, Stephan Ariyan, Elaine Cheng, Antonella Bacchiocchi, Harriet M Kluger, Deepak Narayan, Ruth Halaban

Published in: Journal of Translational Medicine | Issue 1/2010

Login to get access

Abstract

Activating mutations in BRAF kinase are common in melanomas. Clinical trials with PLX4032, the mutant-BRAF inhibitor, show promising preliminary results in patients selected for the presence of V600E mutation. However, activating V600K mutation is the other most common mutation, yet patients with this variant are currently excluded from the PLX4032 trials. Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations.
Appendix
Available only for authorised users
Literature
1.
go back to reference Flaherty K, Puzanov I, Sosman J, Kim K, Ribas A, McArthur G, Lee RJ, Grippo JF, Nolop K, Chapman P: Phase I study of PLX4032: Proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol (Meeting Abstracts). 2009, 27: 9000- Flaherty K, Puzanov I, Sosman J, Kim K, Ribas A, McArthur G, Lee RJ, Grippo JF, Nolop K, Chapman P: Phase I study of PLX4032: Proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol (Meeting Abstracts). 2009, 27: 9000-
2.
go back to reference Uribe P, Wistuba I, González S: BRAF mutation: a frequent event in benign, atypical, and malignant melanocytic lesions of the skin. Am J Dermatopathol. 2003, 25: 365-370. 10.1097/00000372-200310000-00001.PubMedCrossRef Uribe P, Wistuba I, González S: BRAF mutation: a frequent event in benign, atypical, and malignant melanocytic lesions of the skin. Am J Dermatopathol. 2003, 25: 365-370. 10.1097/00000372-200310000-00001.PubMedCrossRef
3.
go back to reference Poynter J, Elder J, Fullen D, Nair R, Soengas M, Johnson T, Redman B, Thomas N, Gruber S: BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res. 2006, 16: 267-273. 10.1097/01.cmr.0000222600.73179.f3.PubMedCrossRef Poynter J, Elder J, Fullen D, Nair R, Soengas M, Johnson T, Redman B, Thomas N, Gruber S: BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res. 2006, 16: 267-273. 10.1097/01.cmr.0000222600.73179.f3.PubMedCrossRef
4.
go back to reference Sala E, Mologni L, Truffa S, Gaetano C, Bollag G, Gambacorti-Passerini C: BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res. 2008, 6: 751-759. 10.1158/1541-7786.MCR-07-2001.PubMedCrossRef Sala E, Mologni L, Truffa S, Gaetano C, Bollag G, Gambacorti-Passerini C: BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res. 2008, 6: 751-759. 10.1158/1541-7786.MCR-07-2001.PubMedCrossRef
5.
go back to reference Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker J, Kluger Y, Sznol M: PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 2010, 23: 190-200.PubMedPubMedCentralCrossRef Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker J, Kluger Y, Sznol M: PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 2010, 23: 190-200.PubMedPubMedCentralCrossRef
6.
go back to reference Pratilas C, Solit D: Targeting the MAPK Pathway: Physiological Feedback and Drug Response. Clin Cancer Res. 2010, 16: 3329-34. 10.1158/1078-0432.CCR-09-3064.PubMedPubMedCentralCrossRef Pratilas C, Solit D: Targeting the MAPK Pathway: Physiological Feedback and Drug Response. Clin Cancer Res. 2010, 16: 3329-34. 10.1158/1078-0432.CCR-09-3064.PubMedPubMedCentralCrossRef
7.
go back to reference Spittle C, Ward M, Nathanson K, Gimotty P, Rappaport E, Brose M, Medina A, Letrero R, Herlyn M, Edwards R: Application of a BRAF pyrosequencing assay for mutation detection and copy number analysis in malignant melanoma. J Mol Diagn. 2007, 9: 464-471. 10.2353/jmoldx.2007.060191.PubMedPubMedCentralCrossRef Spittle C, Ward M, Nathanson K, Gimotty P, Rappaport E, Brose M, Medina A, Letrero R, Herlyn M, Edwards R: Application of a BRAF pyrosequencing assay for mutation detection and copy number analysis in malignant melanoma. J Mol Diagn. 2007, 9: 464-471. 10.2353/jmoldx.2007.060191.PubMedPubMedCentralCrossRef
8.
go back to reference Hay R, MacRae E, Barber D, Khalil M, Demetrick D: BRAF mutations in melanocytic lesions and papillary thyroid carcinoma samples identified using melting curve analysis of polymerase chain reaction products. Arch Pathol Lab Med. 2007, 131: 1361-1367.PubMed Hay R, MacRae E, Barber D, Khalil M, Demetrick D: BRAF mutations in melanocytic lesions and papillary thyroid carcinoma samples identified using melting curve analysis of polymerase chain reaction products. Arch Pathol Lab Med. 2007, 131: 1361-1367.PubMed
9.
go back to reference Willmore-Payne C, Holden J, Tripp S, Layfield L: Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol. 2005, 36: 486-493. 10.1016/j.humpath.2005.03.015.PubMedCrossRef Willmore-Payne C, Holden J, Tripp S, Layfield L: Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol. 2005, 36: 486-493. 10.1016/j.humpath.2005.03.015.PubMedCrossRef
10.
go back to reference Ugurel S, Thirumaran R, Bloethner S, Gast A, Sucker A, Mueller-Berghaus J, Rittgen W, Hemminki K, Becker J, Kumar R, Schadendorf D: B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis. PLoS One. 2007, 2: e236-10.1371/journal.pone.0000236.PubMedPubMedCentralCrossRef Ugurel S, Thirumaran R, Bloethner S, Gast A, Sucker A, Mueller-Berghaus J, Rittgen W, Hemminki K, Becker J, Kumar R, Schadendorf D: B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis. PLoS One. 2007, 2: e236-10.1371/journal.pone.0000236.PubMedPubMedCentralCrossRef
Metadata
Title
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
Authors
Jill C Rubinstein
Mario Sznol
Anna C Pavlick
Stephan Ariyan
Elaine Cheng
Antonella Bacchiocchi
Harriet M Kluger
Deepak Narayan
Ruth Halaban
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2010
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-8-67

Other articles of this Issue 1/2010

Journal of Translational Medicine 1/2010 Go to the issue