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Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma
The discovery of activating BRAF V600E mutations in 50% of all melanoma patients and the development of small molecule BRAF inhibitors looks set to revolutionize the therapy of disseminated melanoma. However, in the recent clinical trial of the BRAF inhibitor, vemurafenib (PLX4032), a significant pe...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248164/ https://www.ncbi.nlm.nih.gov/pubmed/21505227 |
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author | Koomen, John M. Smalley, Keiran S. M. |
author_facet | Koomen, John M. Smalley, Keiran S. M. |
author_sort | Koomen, John M. |
collection | PubMed |
description | The discovery of activating BRAF V600E mutations in 50% of all melanoma patients and the development of small molecule BRAF inhibitors looks set to revolutionize the therapy of disseminated melanoma. However, in the recent clinical trial of the BRAF inhibitor, vemurafenib (PLX4032), a significant percentage of BRAF V600E mutant melanoma patients did not meet the RECIST criteria for a response. Recent work from our lab identified loss of the tumor suppressor phosphatase and tensin homolog (PTEN) as being a possible mediator of intrinsic BRAF inhibitor resistance. In this commentary, we describe the development of a novel mass spectrometry based proteomic screen of Bcl-2 family proteins that was used to delineate the PTEN-dependent differences in apoptosis signaling observed when BRAF was inhibited. We further discuss how use of these sensitive quantitative proteomic methods gives unique insights into the signaling of cancer cells that are not captured through routine biochemical techniques and how this may lead to the development of combination therapy strategies for overcoming intrinsic BRAF inhibitor resistance. |
format | Online Article Text |
id | pubmed-3248164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-32481642012-01-18 Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma Koomen, John M. Smalley, Keiran S. M. Oncotarget Research Perspectives The discovery of activating BRAF V600E mutations in 50% of all melanoma patients and the development of small molecule BRAF inhibitors looks set to revolutionize the therapy of disseminated melanoma. However, in the recent clinical trial of the BRAF inhibitor, vemurafenib (PLX4032), a significant percentage of BRAF V600E mutant melanoma patients did not meet the RECIST criteria for a response. Recent work from our lab identified loss of the tumor suppressor phosphatase and tensin homolog (PTEN) as being a possible mediator of intrinsic BRAF inhibitor resistance. In this commentary, we describe the development of a novel mass spectrometry based proteomic screen of Bcl-2 family proteins that was used to delineate the PTEN-dependent differences in apoptosis signaling observed when BRAF was inhibited. We further discuss how use of these sensitive quantitative proteomic methods gives unique insights into the signaling of cancer cells that are not captured through routine biochemical techniques and how this may lead to the development of combination therapy strategies for overcoming intrinsic BRAF inhibitor resistance. Impact Journals LLC 2011-04-15 /pmc/articles/PMC3248164/ /pubmed/21505227 Text en Copyright: © 2011 Koomen and Smalley http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Perspectives Koomen, John M. Smalley, Keiran S. M. Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
title | Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
title_full | Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
title_fullStr | Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
title_full_unstemmed | Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
title_short | Using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
title_sort | using quantitative proteomic analysis to understand genotype specific intrinsic drug resistance in melanoma |
topic | Research Perspectives |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248164/ https://www.ncbi.nlm.nih.gov/pubmed/21505227 |
work_keys_str_mv | AT koomenjohnm usingquantitativeproteomicanalysistounderstandgenotypespecificintrinsicdrugresistanceinmelanoma AT smalleykeiransm usingquantitativeproteomicanalysistounderstandgenotypespecificintrinsicdrugresistanceinmelanoma |