ArticlePigment cell & melanoma research2020
A genome-wide CRISPR screen identifies FBXO42 involvement in resistance toward MEK inhibition in NRAS-mutant melanoma.
Article in Pigment cell & melanoma research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting ABL kinases overcomes melanoma immune evasion following resistance to MAPK inhibition.Nature communications · 2026Article
- In vivo CRISPR knockout screen identifies Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.Oncogene · 2026Article
- The regulation of protein phosphatase 4 by FBXO42 is required for cancer cell survival.EMBO reports · 2026Article
- Pervasive phenotypic effects of FBXO42 are promoted by regulation of PP4 phosphatase.The EMBO journal · 2026Article
- Selective abrogation of S6K2 identifies lipid homeostasis as a survival vulnerability in MAPK inhibitor-resistantScience translational medicine · 2025Article
- Article
- ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization.Cancers · 2023Article
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer.Cellular & molecular biology letters · 2022Review
- Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells.International journal of molecular sciences · 2022Article
- Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.Frontiers in oncology · 2022Review
- Review
- Many Distinct Ways Lead to Drug Resistance inLife (Basel, Switzerland) · 2021Review
- An Update on the Role of Ubiquitination in Melanoma Development and Therapies.Journal of clinical medicine · 2021Review
- Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.Expert review of precision medicine and drug development · 2021Article
- Visualization Analysis of CRISPR Gene-editing Knowledge Map based on Citespace.Biology bulletin of the Russian Academy of Sciences · 2021Article
- A genome-wide CRISPR screen identifies FBXO42 involvement in resistance toward MEK inhibition in NRAS-mutant melanoma.Pigment cell & melanoma research · 2020Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
NRAS mutations are the most common alterations among RAS isoforms in cutaneous melanoma, with patients harboring these aggressive tumors having a poor prognosis and low survival rate. The main line of treatment for these patients is MAPK pathway-targeted therapies, such as MEK inhibitors, but, unfortunately, the response to these inhibitors is variable due to tumor resistance. Identifying genetic modifiers involved in resistance toward MEK-targeted therapy may assist in the development of new therapeutic strategies, enhancing treatment response and patient survival. Our whole-genome CRISPR-Cas9 knockout screen identified the target Kelch domain-containing F-Box protein 42 (FBXO42) as a factor involved in NRAS-mutant melanoma-acquired resistance to the MEK1/2 inhibitor trametinib. We further show that FBXO42, an E3 ubiquitin ligase, is involved in the TAK1 signaling pathway, possibly prompting an increase in active P38. In addition, we demonstrate that combining trametinib with the TAK1 inhibitor, takinib, is a far more efficient treatment than trametinib alone in NRAS-mutant melanoma cells. Our findings thus show a new pathway involved in NRAS-mutant melanoma resistance and provide new opportunities for novel therapeutic options.
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