ArticleMolecular cancer research : MCR2019
The Antitumor Drugs Trabectedin and Lurbinectedin Induce Transcription-Dependent Replication Stress and Genome Instability.
Article in Molecular cancer research : MCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- The cGAS-STING pathway is a master regulator of OCT4 expression in persistent sarcoma cells and enhances cellular immunotherapy with NK and CIK lymphocytes.Cancer immunology, immunotherapy : CII · 2025Article
- Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Molecular cancer therapeutics · 2025Review
- Patulin and Xestoquinol are inhibitors of DNA topoisomerase 1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors.Cancer research · 2025Article
- Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Preclinical Synergistic Combination Therapy of Lurbinectedin with Irinotecan and 5-Fluorouracil in Pancreatic Cancer.Current oncology (Toronto, Ont.) · 2023Article
- Emerging role for R-loop formation in hepatocellular carcinoma.Genes & genomics · 2023Review
- Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids.Nature reviews. Molecular cell biology · 2022Review
- A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin.Molecular oncology · 2021Article
- SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer.Translational lung cancer research · 2021Article
- Recent developments in the treatment of small cell lung cancer.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Marine Power on Cancer: Drugs, Lead Compounds, and Mechanisms.Marine drugs · 2021Review
- Review
- Development of Marine-Derived Compounds for Cancer Therapy.Marine drugs · 2021Review
- BRCA1 binds TERRA RNA and suppresses R-Loop-based telomeric DNA damage.Nature communications · 2021Article
- Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress.EMBO molecular medicine · 2020Article
- The DNA secondary structures at telomeres and genome instability.Cell & bioscience · 2020Review
- Enriching cancer pharmacology with drugs of marine origin.British journal of pharmacology · 2020Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
R-loops are a major source of replication stress, DNA damage, and genome instability, which are major hallmarks of cancer cells. Accordingly, growing evidence suggests that R-loops may also be related to cancer. Here we show that R-loops play an important role in the cellular response to trabectedin (ET743), an anticancer drug from marine origin and its derivative lurbinectedin (PM01183). Trabectedin and lurbinectedin induced RNA-DNA hybrid-dependent DNA damage in HeLa cells, causing replication impairment and genome instability. We also show that high levels of R-loops increase cell sensitivity to trabectedin. In addition, trabectedin led to transcription-dependent FANCD2 foci accumulation, which was suppressed by RNase H1 overexpression. In yeast, trabectedin and lurbinectedin increased the presence of Rad52 foci, a marker of DNA damage, in an R-loop-dependent manner. In addition to providing new insights into the mechanisms of action of these drugs, our study reveals that R-loops could be targeted by anticancer agents. Given the increasing evidence that R-loops occur all over the genome, the ability of lurbinectedin and trabectedin to act on them may contribute to enhance their efficacy, opening the possibility that R-loops might be a feature shared by specific cancers. IMPLICATIONS: The data presented in this study provide the new concept that R-loops are important cellular factors that contribute to trabectedin and lurbinectedin anticancer activity.
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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.