ArticleNeoplasia (New York, N.Y.)2011
Identification of MET and SRC activation in melanoma cell lines showing primary resistance to PLX4032.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 97 citations in OpenAlex.
- Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma.British journal of cancer · 2017Trial
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- Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles.iScience · 2025Article
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- Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells.Frontiers in oncology · 2023Article
- Indolium 1 Exerts Activity against Vemurafenib-Resistant Melanoma In Vivo.Antioxidants (Basel, Switzerland) · 2022Article
- Targeting of the Lipid Metabolism Impairs Resistance to BRAF Kinase Inhibitor in Melanoma.Frontiers in cell and developmental biology · 2022Article
- CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells.PloS one · 2022Article
- Mitochondrial Metabolism in Melanoma.Cells · 2021Review
- Unbiased High-Throughput Drug Combination Pilot Screening Identifies Synergistic Drug Combinations Effective against Patient-Derived and Drug-Resistant Melanoma Cell Lines.SLAS discovery : advancing life sciences R & D · 2021Article
- Deregulated FASN Expression in BRAF Inhibitor-Resistant Melanoma Cells Unveils New Targets for Drug Combinations.Cancers · 2021Article
- RTK Inhibitors in Melanoma: From Bench to Bedside.Cancers · 2021Review
- Nanocarrier-Based Drug Delivery for Melanoma Therapeutics.International journal of molecular sciences · 2021Review
- Functional Genomic Screening Independently Identifies CUL3 as a Mediator of Vemurafenib Resistance via Src-Rac1 Signaling Axis.Frontiers in oncology · 2020Article
- Developments in the Space of New MAPK Pathway Inhibitors for BRAF-Mutant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Review
- Src-Dependent DBL Family Members Drive Resistance to Vemurafenib in Human Melanoma.Cancer research · 2019Article
- Article
- Review
- A targeted genomic alteration analysis predicts survival of melanoma patients under BRAF inhibitors.Oncotarget · 2019Article
- SRC tyrosine kinase activates the YAP/TAZ axis and thereby drives tumor growth and metastasis.The Journal of biological chemistry · 2019Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PLX4032/vemurafenib is a first-in-class small-molecule BRAF(V600E) inhibitor with clinical activity in patients with BRAF mutant melanoma. Nevertheless, drug resistance develops in treated patients, and strategies to overcome primary and acquired resistance are required. To explore the molecular mechanisms involved in primary resistance to PLX4032, we investigated its effects on cell proliferation and signaling in a panel of 27 genetically characterized patient-derived melanoma cell lines. Cell sensitivity to PLX4032 was dependent on BRAF(V600E) and independent from other gene alterations that commonly occur in melanoma such as PTEN loss, BRAF, and MITF gene amplification. Two cell lines lacking sensitivity to PLX4032 and harboring a different set of genetic alterations were studied as models of primary resistance. Treatment with the MEK inhibitor UO126 but not with PLX4032 inhibited cell growth and ERK activation. Resistance to PLX4032 was maintained after CRAF down-regulation by siRNA indicating alternative activation of MEK-ERK signaling. Genetic characterization by multiplex ligation-dependent probe amplification and analysis of phosphotyrosine signaling by MALDI-TOF mass spectrometry analysis revealed the activation of MET and SRC signaling, associated with the amplification of MET and of CTNNB1 and CCND1 genes, respectively. The combination of PLX4032 with drugs or siRNA targeting MET was effective in inhibiting cell growth and reducing cell invasion and migration in melanoma cells with MET amplification; similar effects were observed after targeting SRC in the other cell line, indicating a role for MET and SRC signaling in primary resistance to PLX4032. Our results support the development of classification of melanoma in molecular subtypes for more effective therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.