ArticleMolecular cancer therapeutics2015
Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 76 citations in OpenAlex.
- Validating TDP1 as an Inhibition Target for Lipophilic Nucleoside Derivative in Human Cells.International journal of molecular sciences · 2025Article
- Transcriptomic Analysis of TDP1-Knockout HEK293A Cells Treated with the TDP1 Inhibitor (Usnic Acid Derivative).International journal of molecular sciences · 2025Article
- Unravelling the molecular mechanistic pathway underlying the anticancer effects of kaempferol in colorectal cancer: a reverse pharmacology network approach.Molecular diversity · 2025Article
- Role of TDP2 in the repair of DNA damage induced by the radiomimetic drug Bleomycin.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome.Science advances · 2024Article
- Minocycline and photodynamic priming significantly improve chemotherapy efficacy in heterotypic spheroids of pancreatic ductal adenocarcinoma.Journal of photochemistry and photobiology. B, Biology · 2024Article
- Enhancement of the Antitumor and Antimetastatic Effect of Topotecan and Normalization of Blood Counts in Mice with Lewis Carcinoma by Tdp1 Inhibitors-New Usnic Acid Derivatives.International journal of molecular sciences · 2024Article
- Cellular resistance mechanisms in cancer and the new approaches to overcome resistance mechanisms chemotherapy.Saudi medical journal · 2023Article
- Influence of Tyrosyl-DNA Phosphodiesterase 1 Inhibitor on the Proapoptotic and Genotoxic Effects of Anticancer Agent Topotecan.Doklady. Biochemistry and biophysics · 2023Article
- Adamantane-Monoterpenoid Conjugates Linked via Heterocyclic Linkers Enhance the Cytotoxic Effect of Topotecan.Molecules (Basel, Switzerland) · 2022Article
- Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids.Nucleic acids research · 2022Article
- Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs.Oncology and therapy · 2021Article
- Dehydroabietylamine-based thiazolidin-4-ones and 2-thioxoimidazolidin-4-ones as novel tyrosyl-DNA phosphodiesterase 1 inhibitors.Molecular diversity · 2021Article
- The influence of an enamine usnic acid derivative (a tyrosyl-DNA phosphodiesterase 1 inhibitor) on the therapeutic effect of topotecan against transplanted tumors in vivo.Clinical & experimental metastasis · 2021Article
- New Advances in the Research of Resistance to Neoadjuvant Chemotherapy in Breast Cancer.International journal of molecular sciences · 2021Review
- Article
- UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer.Cell death & disease · 2021Article
- Potential therapeutic targets shared between leishmaniasis and cancer.Parasitology · 2021Review
- Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance.Biomedicines · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Colorectal cancer is the third most common cancer in the world. Despite surgery, up to 50% of patients relapse with incurable disease. First-line chemotherapy uses the topoisomerase 1 (TOP1) poison irinotecan, which triggers cell death by trapping TOP1 on DNA. The removal of TOP1 peptide from TOP1-DNA breaks is conducted by tyrosyl-DNA phosphodiesterase 1 (TDP1). Despite putative roles for TDP1 and TOP1 in colorectal cancer, their role in cellular and clinical responses to TOP1-targeting therapies remains unclear. Here, we show varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples. TDP1 overexpression or TOP1 depletion is protective. Conversely, TDP1 depletion increases DNA-strand breakage and hypersensitivity to irinotecan in a TOP1-dependent manner, presenting a potential therapeutic opportunity in colorectal cancer. TDP1 protein levels correlate well with mRNA and with TDP1 catalytic activity. However, no correlation is observed between inherent TDP1 or TOP1 levels alone and irinotecan sensitivity, pointing at their limited utility as predictive biomarkers in colorectal cancer. These findings establish TDP1 as a potential therapeutic target for the treatment of colorectal cancer and question the validity of TOP1 or TDP1 on their own as predictive biomarkers for irinotecan response.
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.