ArticleScience translational medicine2019
Identification of DHODH as a therapeutic target in small cell lung cancer.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- A multiplexed in vivo approach to identify driver genes in small cell lung cancer.Cell reports · 2023Pooled it
- Public Transcriptomic Data Mining for SCLC: From Candidate Ma rkers to Therapeutic Exploration.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- DHODH inhibition drives albumin-mediated drug resistance through TERF2IP lactylation-activated macropinosome-mitochondria contact.Nature communications · 2026Article
- Exploring the Role of the LCN2-DHODH Interaction in Mitochondrial Ferroptosis During Sepsis-Induced Myocardial Injury and LPS-Induced HL-1 Cardiomyocyte Injury.International journal of molecular sciences · 2026Article
- NCAPG reprograms glycolytic and lipid metabolism by sustaining glycerophospholipid flux in small-cell lung cancer.Molecular and cellular biochemistry · 2026Article
- Mitochondrial-Localized Keratin 17 Promotes Chemoresistance in Basal-like Pancreatic Cancer.Cancer research · 2026Article
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.Nature metabolism · 2026Article
- Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural and molecular basis for allosteric regulation and catalytic coupling of human phosphoribosylformylglycinamidine synthase.Nature communications · 2026Article
- Recurrent Breast Cancer Cells Depend onbioRxiv : the preprint server for biology · 2025Article
- Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics.Science China. Life sciences · 2025Review
- Dihydroorotate dehydrogenase inhibition activates STING pathway and pyroptosis to enhance NK cell-dependent tumor immunotherapy.Molecular biomedicine · 2025Article
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.iScience · 2025Article
- DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis.Nature communications · 2025Article
- Current and future therapies for small cell lung carcinoma.Journal of hematology & oncology · 2025Review
- From mechanisms to medicine: Ferroptosis as a Therapeutic target in liver disorders.Cell communication and signaling : CCS · 2025Review
- Article
- HIF-2α inhibitors in clear cell renal cell carcinoma: a clinical pharmacy perspective on lipid metabolism, therapeutic management, and resistance strategies.Frontiers in medicine · 2025Review
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Small cell lung cancer (SCLC) is an aggressive lung cancer subtype with extremely poor prognosis. No targetable genetic driver events have been identified, and the treatment landscape for this disease has remained nearly unchanged for over 30 years. Here, we have taken a CRISPR-based screening approach to identify genetic vulnerabilities in SCLC that may serve as potential therapeutic targets. We used a single-guide RNA (sgRNA) library targeting ~5000 genes deemed to encode "druggable" proteins to perform loss-of-function genetic screens in a panel of cell lines derived from autochthonous genetically engineered mouse models (GEMMs) of SCLC, lung adenocarcinoma (LUAD), and pancreatic ductal adenocarcinoma (PDAC). Cross-cancer analyses allowed us to identify SCLC-selective vulnerabilities. In particular, we observed enhanced sensitivity of SCLC cells toward disruption of the pyrimidine biosynthesis pathway. Pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in this pathway, reduced the viability of SCLC cells in vitro and strongly suppressed SCLC tumor growth in human patient-derived xenograft (PDX) models and in an autochthonous mouse model. These results indicate that DHODH inhibition may be an approach to treat SCLC.
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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.