ArticleNucleic acids research2017
Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 61 citations in OpenAlex.
- Maritoclax Overcomes FBW7 Deficiency-Driven Irinotecan Resistance in Colorectal Cancer by Targeting MCL1.Cancer medicine · 2025Article
- Senataxin regulates cisplatin resistance through an R-loop-mediated mechanism in HPV-associated head and neck cancer.iScience · 2025Article
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.Cancer cell international · 2024Review
- Establishment, characterization, and biobanking of 36 pancreatic cancer organoids: prediction of metastasis in resectable pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).International journal of oncology · 2024Review
- A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids.NPJ precision oncology · 2024Article
- Understanding Cancer's Defense against Topoisomerase-Active Drugs: A Comprehensive Review.Cancers · 2024Review
- Bifidobacterium longum SX-1326 ameliorates gastrointestinal toxicity after irinotecan chemotherapy via modulating the P53 signaling pathway and brain-gut axis.BMC microbiology · 2024Article
- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- Radiosensitizing Effects of Irinotecan versus Oxaliplatin Alone and in Combination with 5-Fluorouracil on Human Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- Improving the response to oxaliplatin by targeting chemotherapy-induced CLDN1 in resistant metastatic colorectal cancer cells.Cell & bioscience · 2023Article
- AKT inhibition sensitizes EVI1 expressing colon cancer cells to irinotecan therapy by regulating the Akt/mTOR axis.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Lanthanide (EuInternational journal of molecular sciences · 2022Article
- Epigenetic Regulation Towards Acquired Drug Resistance in Cancer.Sub-cellular biochemistry · 2022Article
- Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis.International journal of molecular sciences · 2021Article
- Mechanistic insights into p53-regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells.Molecular oncology · 2021Article
- Genetic and biological hallmarks of colorectal cancer.Genes & development · 2021Review
- TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance.Biomedicines · 2021Review
- Article
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 2 countries.
Funding
Abstract
The topoisomerase I (TOP1) inhibitor irinotecan triggers cell death by trapping TOP1 on DNA, generating cytotoxic protein-linked DNA breaks (PDBs). Despite its wide application in a variety of solid tumors, the mechanisms of cancer cell resistance to irinotecan remains poorly understood. Here, we generated colorectal cancer (CRC) cell models for irinotecan resistance and report that resistance is neither due to downregulation of the main cellular target of irinotecan TOP1 nor upregulation of the key TOP1 PDB repair factor TDP1. Instead, the faster repair of PDBs underlies resistance, which is associated with perturbed histone H4K16 acetylation. Subsequent treatment of irinotecan-resistant, but not parental, CRC cells with histone deacetylase (HDAC) inhibitors can effectively overcome resistance. Immunohistochemical analyses of CRC tissues further corroborate the importance of histone H4K16 acetylation in CRC. Finally, the resistant clones exhibit cross-resistance with oxaliplatin but not with ionising radiation or 5-fluoruracil, suggesting that the latter two could be employed following loss of irinotecan response. These findings identify perturbed chromatin acetylation in irinotecan resistance and establish HDAC inhibitors as potential therapeutic means to overcome resistance.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.