ArticleMolecular systems biology2015
Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 106 citations in OpenAlex.
- Mechanistic modeling reveals a configurable AP-1 network governing cell-state heterogeneity and adaptive plasticity in melanoma cells.Cell reports · 2026Article
- Integrative multi-omics defines melanoma drug response networks and ARID1A-dependent resistance mechanisms.Molecular systems biology · 2026Article
- Targeting polyamine metabolism and ferroptosis enhances the efficacy of KRAS-targeted therapy depending on KEAP1 status.Nature communications · 2025Article
- Fyn inhibition by TAE684: A synergistic strategy to suppress melanoma and reverse vemurafenib resistance.Cell death & disease · 2025Article
- Phenotype switching in highly invasive resistant to vemurafenib and cobimetinib melanoma cells.Cell communication and signaling : CCS · 2025Article
- Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer.British journal of cancer · 2025Article
- BRAFClinical and translational medicine · 2025Article
- Characterization of two melanoma cell lines resistant to BRAF/MEK inhibitors (vemurafenib and cobimetinib).Cell communication and signaling : CCS · 2024Article
- Article
- Small-molecule inhibition of MAP2K4 is synergistic with RAS inhibitors inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- OncogenicNeural regeneration research · 2023Article
- Localized immune surveillance of primary melanoma in the skin deciphered through executable modeling.Science advances · 2023Article
- Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition.Cancer research · 2023Article
- SRC-RAC1 signaling drives drug resistance to BRAF inhibition in de-differentiated cutaneous melanomas.NPJ precision oncology · 2022Article
- AP-1 transcription factor network explains diverse patterns of cellular plasticity in melanoma cells.Cell reports · 2022Article
- Review
- Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies.Antioxidants (Basel, Switzerland) · 2021Review
- Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids.Nature communications · 2021Article
- Rapid signaling reactivation after targeted BRAF inhibition predicts the proliferation of individual melanoma cells from an isogenic population.Scientific reports · 2021Article
- Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1.Nature communications · 2021Article
4 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
6 authors at 3 institutions in 1 country.
Funding
Abstract
Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAF(V) (600E) melanoma. Adaptive responses to RAF/MEK inhibition occur on a timescale of hours to days, involve homeostatic responses that reactivate MAP kinase signaling and compensatory mitogenic pathways, and attenuate the anti-tumor effects of RAF/MEK inhibitors. We profile adaptive responses across a panel of melanoma cell lines using multiplex biochemical measurement, single-cell assays, and statistical modeling and show that adaptation involves at least six signaling cascades that act to reduce drug potency (IC50) and maximal effect (i.e., Emax ≪ 1). Among these cascades, we identify a role for JNK/c-Jun signaling in vemurafenib adaptation and show that RAF and JNK inhibitors synergize in cell killing. This arises because JNK inhibition prevents a subset of cells in a cycling population from becoming quiescent upon vemurafenib treatment, thereby reducing drug Emax. Our findings demonstrate the breadth and diversity of adaptive responses to RAF/MEK inhibition and a means to identify which steps in a signaling cascade are most predictive of phenotypic response.
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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.