ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven Sensitivity in Urothelial Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Click-code-seq reveals strand biases of DNA oxidation and depurination in human genome.Nature chemical biology · 2026Article
- Irofulven and RSL3 synergistically target ferroptosis-related gene PTGR1 to treat head and neck squamous cell carcinoma.Open life sciences · 2026Article
- Assessing expression patterns of PTGR1, a potential biomarker for acylfulven sensitivity in urothelial carcinoma.Scientific reports · 2024Article
- Impact of DNA Repair Deficiency in the Evolving Treatment Landscape of Bladder Cancer.Current urology reports · 2024Review
- ERCC2 mutations alter the genomic distribution pattern of somatic mutations and are independently prognostic in bladder cancer.Cell genomics · 2024Article
- Molecular profiling of a bladder cancer with very high tumour mutational burden.Cell death discovery · 2024Article
- Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting.NPJ precision oncology · 2024Article
- Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes.Nature communications · 2024Article
- Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Nucleotide excision repair deficiency is a targetable therapeutic vulnerability in clear cell renal cell carcinoma.Scientific reports · 2023Article
- Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies.Molecular cancer therapeutics · 2023Article
- Orellanine: From Fungal Origin to a Potential Future Cancer Treatment.Journal of natural products · 2023Review
- Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non-Muscle-Invasive Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Alteration of the Nucleotide Excision Repair (NER) Pathway in Soft Tissue Sarcoma.International journal of molecular sciences · 2022Article
- Review
- Pan-cancer analysis of necroptosis-related gene signature for the identification of prognosis and immune significance.Discover oncology · 2022Article
- Prognostic impact of Schlafen 11 in bladder cancer patients treated with platinum-based chemotherapy.Cancer science · 2022Article
- Detection of Molecular Signatures of Homologous Recombination Deficiency in Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Morning for Irofulven, What Could be fiNER?Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
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30 authors at 14 institutions in 3 countries.
Funding
Abstract
purposeCisplatin-based chemotherapy is a first-line treatment for muscle-invasive and metastatic urothelial cancer. Approximately 10% of bladder urothelial tumors have a somatic missense mutation in the nucleotide excision repair (NER) gene, EXPERIMENTAL
designWe used a series of NER-proficient and NER-deficient preclinical tumor models to test sensitivity to irofulven, an abandoned anticancer agent. In addition, we used available clinical and sequencing data from multiple urothelial tumor cohorts to develop and validate a composite mutational signature of
resultsWe identified a novel synthetic lethal relationship between tumor NER deficiency and sensitivity to irofulven. Irofulven specifically targets cells with inactivation of the transcription-coupled NER (TC-NER) pathway and leads to robust responses
conclusionsTumor NER deficiency confers sensitivity to irofulven, a previously abandoned anticancer agent, with minimal activity in NER-proficient cells. A composite mutational signature of NER deficiency may be useful in identifying patients likely to respond to NER-targeting agents, including cisplatin and irofulven.
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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.