ArticleCancers2023
Vemurafenib and Dabrafenib Downregulates RIPK4 Level.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed.
- RIPK4 is associated with altered bioenergetics and invasive in melanoma three-dimensional models.Scientific reports · 2026Article
- RIPK4 function interferes with melanoma cell adhesion and metastasis.Molecular oncology · 2026Article
- Development of new liposomal formulations of quercetin - in vitro study.Scientific reports · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- TMT proteomics reveals that miR-425-5p promotes proliferation and metastasis of malignant melanoma by inhibiting SCARA5.Cancer cell international · 2026Article
- Inhibition of the RIPK4 enhances suppression of human melanoma growth through vitamin D signaling.Molecular and cellular endocrinology · 2025Article
- Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity.Basic & clinical pharmacology & toxicology · 2025Article
- RIPK4 Downregulation Reduces ABCG2 Expression, Increasing BRAF-Mutated Melanoma Cell Susceptibility to Cisplatin- and Doxorubicin-Induced Apoptosis.Biomolecules · 2024Article
- The involvement of RIPK4 in TNF-α-stimulated IL-6 and IL-8 production by melanoma cells.Journal of cancer research and clinical oncology · 2024Article
- Using tumor habitat-derived radiomic analysis during pretreatmentCancer imaging : the official publication of the International Cancer Imaging Society · 2024Article
- Lysicamine Reduces Protein Kinase B (AKT) Activation and Promotes Necrosis in Anaplastic Thyroid Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Protein Kinases and their Inhibitors Implications in Modulating Disease Progression.The protein journal · 2023Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Vemurafenib and dabrafenib are BRAF kinase inhibitors (BRAFi) used for the treatment of patients with melanoma carrying the V600E BRAF mutation. However, melanoma cells develop resistance to both drugs when used as monotherapy. Therefore, mechanisms of drug resistance are investigated, and new molecular targets are sought that could completely inhibit melanoma progression. Since receptor-interacting protein kinase (RIPK4) probably functions as an oncogene in melanoma and its structure is similar to the BRAF protein, we analyzed the impact of vemurafenib and dabrafenib on RIPK4 in melanomas. The in silico study confirmed the high similarity of BRAF kinase domains to the RIPK4 protein at both the sequence and structural levels and suggests that BRAFi could directly bind to RIPK4 even more strongly than to ATP. Furthermore, BRAFi inhibited ERK1/2 activity and lowered RIPK4 protein levels in BRAF-mutated melanoma cells (A375 and WM266.4), while in wild-type BRAF cells (BLM and LoVo), both inhibitors decreased the level of RIPK4 and enhanced ERK1/2 activity. The phosphorylation of phosphatidylethanolamine binding protein 1 (PEBP1)-a suppressor of the BRAF/MEK/ERK pathway-via RIPK4 observed in pancreatic cancer did not occur in melanoma. Neither downregulation nor upregulation of RIPK4 in BRAF- mutated cells affected PEBP1 levels or the BRAF/MEK/ERK pathway. The downregulation of RIPK4 inhibited cell proliferation and the FAK/AKT pathway, and increased BRAFi efficiency in WM266.4 cells. However, the silencing of RIPK4 did not induce apoptosis or necroptosis. Our study suggests that RIPK4 may be an off-target for BRAF inhibitors.
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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.