ArticlePigment cell & melanoma research2013
Selective RAF inhibitor impairs ERK1/2 phosphorylation and growth in mutant NRAS, vemurafenib-resistant melanoma cells.
Article in Pigment cell & melanoma research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- Targeting RAF dimers in RAS mutant tumors: From biology to clinic.Acta pharmaceutica Sinica. B · 2024Review
- Inhibition of TGF-β signaling, invasion, and growth of cutaneous squamous cell carcinoma by PLX8394.Oncogene · 2023Article
- MALAT1 as master regulator of biomarkers predictive of pan-cancer multi-drug resistance in the context of recalcitrant NRAS signaling pathway identified using systems-oriented approach.Scientific reports · 2022Article
- A Review of the Molecular Pathways Involved in Resistance to BRAF Inhibitors in Patients with Advanced-Stage Melanoma.Medical science monitor : international medical journal of experimental and clinical research · 2020Review
- Targeting CDC7 sensitizes resistance melanoma cells to BRAFScientific reports · 2019Article
- A novel RFLP-ARMS TaqMan PCR-based method for detecting the BRAF V600E mutation in melanoma.Oncology letters · 2018Article
- Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations.Oncogene · 2018Review
- Response and Resistance to Paradox-Breaking BRAF Inhibitor in MelanomasMolecular cancer therapeutics · 2018Article
- New perspectives for targeting RAF kinase in human cancer.Nature reviews. Cancer · 2017Review
- Overcoming resistance to single-agent therapy for oncogenicOncotarget · 2017Article
- Finding melanoma drugs through a probabilistic knowledge graph.PeerJ. Computer science · 2017Article
- A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner.Oncotarget · 2016Article
- The transcription factor RUNX2 regulates receptor tyrosine kinase expression in melanoma.Oncotarget · 2016Article
- Nevospheres from neurocutaneous melanocytosis cells show reduced viability when treated with specific inhibitors of NRAS signaling pathway.Neuro-oncology · 2016Article
- Review
- Article
- MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy.Drug design, development and therapy · 2016Review
- Fibroblast-derived neuregulin 1 promotes compensatory ErbB3 receptor signaling in mutant BRAF melanoma.The Journal of biological chemistry · 2015Article
- XL888 Limits Vemurafenib-Induced Proliferative Skin Events by Suppressing Paradoxical MAPK Activation.The Journal of investigative dermatology · 2015Article
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The RAF inhibitor vemurafenib achieves remarkable clinical responses in mutant BRAF melanoma patients. However, vemurafenib is burdened by acquired drug resistance and by the side effects associated with its paradoxical activation of the ERK1/2 pathway in wild-type BRAF cells. This paradoxical effect has driven the development of a new class of RAF inhibitors. Here, we tested one of these selective, non-paradox-inducing RAF inhibitors termed paradox-breaker-04 (PB04) or PLX7904. Consistent with its design, PB04 is able to efficiently inhibit activation of ERK1/2 in mutant BRAF melanoma cells but does not hyperactivate ERK1/2 in mutant RAS-expressing cells. Importantly, PB04 inhibited ERK1/2 phosphorylation in mutant BRAF melanoma cells with acquired resistance to vemurafenib/PLX4720 that is mediated by a secondary mutation in NRAS. Consistent with ERK1/2 reactivation driving the re-acquisition of malignant properties, PB04 promoted apoptosis and inhibited entry into S phase and anchorage-independent growth in mutant N-RAS-mediated vemurafenib-resistant cells. These data indicate that paradox-breaker RAF inhibitors may be clinically effective as a second-line option in a cohort of acquired vemurafenib-resistant patients.
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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.