ArticleMolecular & cellular proteomics : MCP2014
Evaluating melanoma drug response and therapeutic escape with quantitative proteomics.
Article in Molecular & cellular proteomics : MCP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
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- Dose-escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF-mutant solid tumors.Cancer · 2023Article
- Deciphering Phenotypes from Protein Biomarkers for Translational Research with PIPER.Journal of proteome research · 2023Article
- A highly multiplexed quantitative phosphosite assay for biology and preclinical studies.Molecular systems biology · 2021Article
- Targeted mass spectrometry-based assays enable multiplex quantification of receptor tyrosine kinase, MAP Kinase, and AKT signaling.Cell reports methods · 2021Article
- SATB2 induction of a neural crest mesenchyme-like program drives melanoma invasion and drug resistance.eLife · 2021Article
- Emerging strategies to treat rare and intractable subtypes of melanoma.Pigment cell & melanoma research · 2021Review
- Review
- Inhibitors of HSP90 in melanoma.Apoptosis : an international journal on programmed cell death · 2020Review
- 17-Aminogeldanamycin selectively diminishes IRE1α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAFApoptosis : an international journal on programmed cell death · 2019Article
- Phosphoprotein patterns predict trametinib responsiveness and optimal trametinib sensitisation strategies in melanoma.Cell death and differentiation · 2019Article
- Combined BRAF and HSP90 Inhibition in Patients with UnresectableClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors.Molecular systems biology · 2018Article
- Acetylsalicylic Acid Governs the Effect of Sorafenib inClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer.Journal of proteome research · 2018Article
- Article
- Proteomic interrogation of HSP90 and insights for medical research.Expert review of proteomics · 2017Review
- Intercellular Resistance to BRAF Inhibition Can Be Mediated by Extracellular Vesicle-Associated PDGFRβ.Neoplasia (New York, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The evolution of cancer therapy into complex regimens with multiple drugs requires novel approaches for the development and evaluation of companion biomarkers. Liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) is a versatile platform for biomarker measurement. In this study, we describe the development and use of the LC-MRM platform to study the adaptive signaling responses of melanoma cells to inhibitors of HSP90 (XL888) and MEK (AZD6244). XL888 had good anti-tumor activity against NRAS mutant melanoma cell lines as well as BRAF mutant cells with acquired resistance to BRAF inhibitors both in vitro and in vivo. LC-MRM analysis showed HSP90 inhibition to be associated with decreased expression of multiple receptor tyrosine kinases, modules in the PI3K/AKT/mammalian target of rapamycin pathway, and the MAPK/CDK4 signaling axis in NRAS mutant melanoma cell lines and the inhibition of PI3K/AKT signaling in BRAF mutant melanoma xenografts with acquired vemurafenib resistance. The LC-MRM approach targeting more than 80 cancer signaling proteins was highly sensitive and could be applied to fine needle aspirates from xenografts and clinical melanoma specimens (using 50 μg of total protein). We further showed MEK inhibition to be associated with signaling through the NFκB and WNT signaling pathways, as well as increased receptor tyrosine kinase expression and activation. Validation studies identified PDGF receptor β signaling as a potential escape mechanism from MEK inhibition, which could be overcome through combined use of AZD6244 and the PDGF receptor inhibitor, crenolanib. Together, our studies show LC-MRM to have unique value as a platform for the systems level understanding of the molecular mechanisms of drug response and therapeutic escape. This work provides the proof-of-principle for the future development of LC-MRM assays for monitoring drug responses in the clinic.
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Registered trials
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.