ArticleJournal of experimental & clinical cancer research : CR2022
Wild-type IDH1 inhibition enhances chemotherapy response in melanoma.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Targeting chordoma via an isocitrate dehydrogenase-1-dependent susceptibility to redox metabolism.Acta neuropathologica · 2026Article
- Article
- A ketogenic diet sensitizes pancreatic cancer to glutamine metabolism inhibitors.Cell reports. Medicine · 2026Article
- Convallatoxin ameliorates fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis by targeting IDH1.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Melanoma resists chemotherapy through an adaptive mitochondrial response.Journal of experimental & clinical cancer research : CR · 2026Article
- Advantages of MelArray over Oncomine Focus Assay for Mutation Analysis in Melanoma.Medicina (Kaunas, Lithuania) · 2026Article
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Targeting IDH1 mutation-driven Nrf2 signaling to suppress malignant behavior in fibrosarcoma cells.Toxicological research · 2025Article
- Inactivation of the SLC25A1 gene during embryogenesis induces a unique senescence program controlled by p53.Cell death and differentiation · 2025Article
- Melanoma genomics - will we go beyond BRAF in clinics?Journal of cancer research and clinical oncology · 2024Review
- IDH1 Inhibition Potentiates Chemotherapy Efficacy in Pancreatic Cancer.Cancer research · 2024Article
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Current Approaches to Epigenetic Therapy.Epigenomes · 2023Review
- Clinical Utility of Ivosidenib in the Treatment of IDH1-Mutant Cholangiocarcinoma: Evidence To Date.Cancer management and research · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAlternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme protects cancer cells under metabolic stress, including nutrient limited conditions in the tumor microenvironment. Specifically, IDH1 generates NADPH to maintain redox homeostasis and produces α-ketoglutarate to support mitochondrial function through anaplerosis. Herein, the role of wtIDH1 in melanoma is further explored.
methodsThe expression of wtIDH1 was determined by qRT-PCR, and Western blot in melanoma cell lines and the effect of wtIDH1 on metabolic reprogramming in melanoma was interrogated by LC-MS. The impact of wtIDH1 inhibition alone and in combination with chemotherapy was determined in cell culture and mouse melanoma models.
resultsMelanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironment in natura. Thus, similar findings were replicated in murine models of melanoma. In light of the impact of wtIDH1 inhibition on oxidative stress, enzyme blockade was synergistic with conventional anti-melanoma chemotherapy in pre-clinical models.
conclusionsThese results demonstrate the clinical potential of wtIDH1 inhibition as a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma. Schematic shows increased wild-type IDH1 expression and activity as an adaptive response to metabolic stress induced by chemotherapy.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.