publication . Article . Other literature type . 2017

An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer

Piro Lito; Piro Lito; Gouri Nanjangud; Trang Thi Mai; Yaohua Xue; Yaohua Xue; G. J. Riely; Ulrika Stierner; Alberto Vides; Fabiola Cechhi; ...
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Open Access English
  • Published: 17 Jul 2017 Journal: Nature medicine, volume 23, issue 8, pages 929-937 (issn: 1078-8956, eissn: 1546-170X, Copyright policy)
Abstract
The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAFamp) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment. The evolutionary selection of BRAFamp was determined by the fitness th...
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doi: 10.1038/nm.4369
pmc: PMC5696266
pmid: 28714990
Subjects
free text keywords: Article, General Biochemistry, Genetics and Molecular Biology, General Medicine, Bioinformatics, Cancer, medicine.disease, medicine, Melanoma, Gene duplication, Oncogene, Mutant, Cancer research, Biology, Kinase, MAPK/ERK pathway, Targeted therapy, medicine.medical_treatment
Related Organizations
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Funded by
NIH| Elucidating the regulation of mitosis by BRAF V600E in lung cancer
Project
Elucidating the regulation of mitosis by BRAF V600E in lung cancer
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5K08CA191082-02
  • Funding stream: NATIONAL CANCER INSTITUTE
, NIH| MOUSE GENETICS
Project
MOUSE GENETICS
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
, NIH| MSKCC Pilot Center for Precision Disease Modeling
Project
MSKCC Pilot Center for Precision Disease Modeling
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U54OD020355-04
  • Funding stream: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
, NIH| Weill Cornell/Rockefeller/Sloan-Kettering MST Program
Project
Weill Cornell/Rockefeller/Sloan-Kettering MST Program
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32GM007739-30
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Download fromView all 3 versions
Europe PubMed Central
Article . 2017
Provider: PubMed Central
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http://dx.doi.org/10.1038/nm.4...
Other literature type . 2017
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48 references, page 1 of 4

Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014; 511: 543-550 [OpenAIRE] [PubMed] [DOI]

Davies, H. Mutations of the BRAF gene in human cancer. Nature. 2002; 417: 949-954 [OpenAIRE] [PubMed] [DOI]

Flaherty, KT. Inhibition of mutated, activated BRAF in metastatic melanoma. The New England journal of medicine. 2010; 363: 809-819 [OpenAIRE] [PubMed] [DOI]

Planchard, D. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. The Lancet Oncology. 2016; 17: 642-650 [OpenAIRE] [PubMed] [DOI]

Flaherty, KT. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. The New England journal of medicine. 2012; 367: 1694-1703 [OpenAIRE] [PubMed] [DOI]

Larkin, J. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. The New England journal of medicine. 2014; 371: 1867-1876 [PubMed] [DOI]

Long, GV. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. The New England journal of medicine. 2014; 371: 1877-1888 [OpenAIRE] [PubMed] [DOI]

Planchard, D. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. The Lancet Oncology. 2016; 17: 984-993 [OpenAIRE] [PubMed] [DOI]

Poulikakos, PI. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011; 480: 387-390 [OpenAIRE] [PubMed] [DOI]

Shi, H. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nature communications. 2012; 3: 724 [OpenAIRE] [DOI]

Das Thakur, M. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013; 494: 251-255 [OpenAIRE] [PubMed] [DOI]

Shi, H. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer discovery. 2014; 4: 80-93 [OpenAIRE] [PubMed] [DOI]

Lito, P, Rosen, N, Solit, DB. Tumor adaptation and resistance to RAF inhibitors. Nature medicine. 2013; 19: 1401-1409 [OpenAIRE] [DOI]

Bollag, G. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010; 467: 596-599 [OpenAIRE] [PubMed] [DOI]

Lito, P. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer cell. 2012; 22: 668-682 [OpenAIRE] [PubMed] [DOI]

48 references, page 1 of 4
Related research
Abstract
The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAFamp) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment. The evolutionary selection of BRAFamp was determined by the fitness th...
Read more
doi: 10.1038/nm.4369
pmc: PMC5696266
pmid: 28714990
Subjects
free text keywords: Article, General Biochemistry, Genetics and Molecular Biology, General Medicine, Bioinformatics, Cancer, medicine.disease, medicine, Melanoma, Gene duplication, Oncogene, Mutant, Cancer research, Biology, Kinase, MAPK/ERK pathway, Targeted therapy, medicine.medical_treatment
Related Organizations
View more
Funded by
NIH| Elucidating the regulation of mitosis by BRAF V600E in lung cancer
Project
Elucidating the regulation of mitosis by BRAF V600E in lung cancer
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5K08CA191082-02
  • Funding stream: NATIONAL CANCER INSTITUTE
, NIH| MOUSE GENETICS
Project
MOUSE GENETICS
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
, NIH| MSKCC Pilot Center for Precision Disease Modeling
Project
MSKCC Pilot Center for Precision Disease Modeling
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U54OD020355-04
  • Funding stream: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
, NIH| Weill Cornell/Rockefeller/Sloan-Kettering MST Program
Project
Weill Cornell/Rockefeller/Sloan-Kettering MST Program
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32GM007739-30
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Download fromView all 3 versions
Europe PubMed Central
Article . 2017
Provider: PubMed Central
Nature Medicine
Article
Provider: UnpayWall
http://dx.doi.org/10.1038/nm.4...
Other literature type . 2017
Provider: Datacite
Nature Medicine
Article
Provider: Microsoft Academic Graph
48 references, page 1 of 4

Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014; 511: 543-550 [OpenAIRE] [PubMed] [DOI]

Davies, H. Mutations of the BRAF gene in human cancer. Nature. 2002; 417: 949-954 [OpenAIRE] [PubMed] [DOI]

Flaherty, KT. Inhibition of mutated, activated BRAF in metastatic melanoma. The New England journal of medicine. 2010; 363: 809-819 [OpenAIRE] [PubMed] [DOI]

Planchard, D. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. The Lancet Oncology. 2016; 17: 642-650 [OpenAIRE] [PubMed] [DOI]

Flaherty, KT. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. The New England journal of medicine. 2012; 367: 1694-1703 [OpenAIRE] [PubMed] [DOI]

Larkin, J. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. The New England journal of medicine. 2014; 371: 1867-1876 [PubMed] [DOI]

Long, GV. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. The New England journal of medicine. 2014; 371: 1877-1888 [OpenAIRE] [PubMed] [DOI]

Planchard, D. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. The Lancet Oncology. 2016; 17: 984-993 [OpenAIRE] [PubMed] [DOI]

Poulikakos, PI. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011; 480: 387-390 [OpenAIRE] [PubMed] [DOI]

Shi, H. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nature communications. 2012; 3: 724 [OpenAIRE] [DOI]

Das Thakur, M. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013; 494: 251-255 [OpenAIRE] [PubMed] [DOI]

Shi, H. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer discovery. 2014; 4: 80-93 [OpenAIRE] [PubMed] [DOI]

Lito, P, Rosen, N, Solit, DB. Tumor adaptation and resistance to RAF inhibitors. Nature medicine. 2013; 19: 1401-1409 [OpenAIRE] [DOI]

Bollag, G. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010; 467: 596-599 [OpenAIRE] [PubMed] [DOI]

Lito, P. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer cell. 2012; 22: 668-682 [OpenAIRE] [PubMed] [DOI]

48 references, page 1 of 4
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