ArticleThe Journal of investigative dermatology2020
Targeting PHGDH Upregulation Reduces Glutathione Levels and Resensitizes Resistant NRAS-Mutant Melanoma to MAPK Kinase Inhibition.
Article in The Journal of investigative dermatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- CRISPR-Based Gene Dependency Screens Reveal Mechanism of BRAF Inhibitor Resistance in Anaplastic Thyroid Cancer.Molecular carcinogenesis · 2026Article
- Metabolic reprogramming-a breakthrough point in overcoming resistance to BRAF mutant melanoma targeted therapy (Review).Oncology letters · 2026Review
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Metabolic Reprogramming in Melanoma: An Epigenetic Point of View.Pharmaceuticals (Basel, Switzerland) · 2025Review
- PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability.Cancer research · 2025Article
- Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis.International journal of molecular sciences · 2024Review
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Integration of Computational Pipeline to Streamline Efficacious Drug Nomination and Biomarker Discovery in Glioblastoma.Cancers · 2024Article
- MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability.bioRxiv : the preprint server for biology · 2024Article
- Article
- p63 orchestrates serine and one carbon metabolism enzymes expression in head and neck cancer.Biology direct · 2023Article
- Serine Metabolic Reprogramming in Tumorigenesis, Tumor Immunity, and Clinical Treatment.Advances in nutrition (Bethesda, Md.) · 2023Review
- Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers.Biomarker research · 2023Review
- Melanogenesis and the Targeted Therapy of Melanoma.Biomolecules · 2022Review
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.Cancers · 2022Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Melanomas frequently harbor activating NRAS mutations leading to activation of MAPK kinase (MEK) and extracellular signal-regulated kinase 1/2 signaling; however, the clinical efficacy of inhibitors to this pathway is limited by resistance. Tumors rewire metabolic pathways in response to stress signals such as targeted inhibitors and drug resistance, but most therapy-resistant preclinical models are generated in conditions that lack physiological metabolism. We generated human NRAS-mutant melanoma xenografts that were resistant to the MEK inhibitor (MEKi) PD0325901 in vivo. MEKi-resistant cells showed cross-resistance to the structurally distinct MEKi trametinib and elevated extracellular signal-regulated kinase 1/2 phosphorylation and downstream signaling. Additionally, we observed upregulation of the serine synthesis pathway and PHGDH, a key enzyme in this pathway. Suppressing PHGDH in MEKi-resistant cells together with MEKi treatment decreased oxidative stress tolerance and cell proliferation. Together, our data suggest targeting PHGDH as a potential strategy in overcoming MEKi resistance.
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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.