ArticleOncotarget2017
Camptothecin resistance is determined by the regulation of topoisomerase I degradation mediated by ubiquitin proteasome pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 25 citations in OpenAlex.
- Protease inhibition: breaking the barriers of chemoresistance in cancer.Molecular biology reports · 2026Review
- Proteasome inhibitor, ixazomib prevents topoisomerase-I degradation and reverses irinotecan resistance in colorectal cancer.Molecular oncology · 2026Article
- Article
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- Camptothecin in Cancer Therapy: Current Challenges and Emerging Strategies with Nanoemulsions.Pharmaceutics · 2025Review
- Sequential Antibody-Drug Conjugate Therapy in Patients With Metastatic Breast Cancer Treated With Sacituzumab Govitecan and Trastuzumab Deruxtecan.JCO precision oncology · 2025Article
- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance.International journal of molecular sciences · 2023Review
- Identifying Novel Actionable Targets in Colon Cancer.Biomedicines · 2021Review
- Article
- Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.DNA repair · 2020Review
- ATM antagonizes NHEJ proteins assembly and DNA-ends synapsis at single-ended DNA double strand breaks.Nucleic acids research · 2020Article
- Article
- PARP-1-dependent RND1 transcription induced by topoisomerase I cleavage complexes confers cellular resistance to camptothecin.Cell death & disease · 2018Article
- Developing a Phosphospecific IHC Assay as a Predictive Biomarker for Topoisomerase I Inhibitors.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?American journal of cancer research · 2017Review
- Characterization of Camptothecin-induced Genomic Changes in the Camptothecin-resistant T-ALL-derived Cell Line CPT-K5.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
Proteasomal degradation of topoisomerase I (topoI) is one of the most remarkable cellular phenomena observed in response to camptothecin (CPT). Importantly, the rate of topoI degradation is linked to CPT resistance. Formation of the topoI-DNA-CPT cleavable complex inhibits DNA re-ligation resulting in DNA-double strand break (DSB). The degradation of topoI marks the first step in the ubiquitin proteasome pathway (UPP) dependent DNA damage response (DDR). Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1. A higher basal level of topoI-pS10 ensures rapid topoI degradation leading to CPT resistance. Importantly, PTEN regulates DNA-PKcs kinase activity in this pathway and PTEN deletion ensures DNA-PKcs dependent higher topoI-pS10, rapid topoI degradation and CPT resistance.
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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.