ReviewAmerican journal of cancer research2017
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?
Review in American journal of cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
135 citing papers in PubMed, 2 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Clinical Outcomes and Effectiveness of CRLX101 for Solid Tumors: A Systematic Review and Meta-analysis.Current medicinal chemistry · 2025Pooled it
- A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways.Medical oncology (Northwood, London, England) · 2024Pooled it
- Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors.Cancer chemotherapy and pharmacology · 2020Trial
- Measurement of NLG207 (formerly CRLX101) nanoparticle-bound and released camptothecin in human plasma.Journal of pharmaceutical and biomedical analysis · 2020Trial
- PARG inhibition reduces ssDNA levels and limits RPA loading upon replication fork collapse.EMBO reports · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Liposomal Encapsulation of Camptothecin/Carboxymethyl-β-Cyclodextrin Complexes: Stability, Solubility and Cytotoxicity.International journal of molecular sciences · 2026Article
- CGF induces ROS-mediated metabolic reprogramming and mitochondrial dysfunction to suppress colorectal cancer progression.iScience · 2026Article
- Metabolomic Study of 7-Ethyl-9-(Metabolites · 2026Article
- Blue Fluorescent Siloxytecans Exhibit Potent Anticancer Activity and Enable Direct Real-Time Quantification of Intracellular Uptake.ACS bio & med chem Au · 2026Article
- Harnessing Endophytic Fungi as a Sustainable Source of Novel Anticancer Agents: Opportunities, Challenges, and Future Directions.Molecules (Basel, Switzerland) · 2026Review
- Identification of low-toxicity DNA topoisomerase I inhibitors with potential blood-brain barrier penetrability for glioblastoma therapy: structure-based virtual screening reveals promising novel Scaffolds.Molecular diversity · 2026Article
- A Novel FGFR3-Targeting Antibody-Drug Conjugate Induces Tumor Cell Apoptosis through the cGAS-STING Pathway in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- Pathophysiological and Etiological Corroborations for the Mechanistic Design of Intranasal Therapies in Glioblastoma Multiforme.Current pharmaceutical design · 2026Review
- Breast cancer pathogenesis, diagnosis and treatment: a comprehensive review.Frontiers in oncology · 2026Review
- Untargeted metabolomics approaches challenge the nutri-score FOPNL system in soluble cocoa products.NPJ science of food · 2025Article
- Preclinical Pharmacokinetic, Pharmacodynamic, and Safety Profile of OBI-992: A Novel TROP2-Targeted Antibody-Drug Conjugate.Molecular cancer therapeutics · 2025Article
- Albumin-based nanoparticles encapsulating SN-38 demonstrate superior antitumor efficacy compared to irinotecan.Drug delivery · 2025Article
- Investigating the Epigenetic Therapeutic Potential of Natural Compounds in Cancer.International journal of molecular sciences · 2025Review
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Camptothecin (CPT) was discovered from plant extracts more than 60 years ago. Since then, only two CPT analogues (irinotecan and topotecan) have been approved for cancer treatment, although several thousand CPT derivatives have been synthesized and many of them were actively studied in our research community over the past 6+ decades. In this review article, we briefly summarize: (1) the discovery and early development of CPTs, (2) the recognized CPT mechanism of action (MOA), (3) the synthesis of CPT and CPT analogues, and (4) the structure-activity relationship (SAR) of CPT and its analogues. Next, we provide evidence that certain CPT analogues can exert improved efficacy with low toxicity independently of topoisomerase I (Top1) inhibition; instead, these CPT analogues use novel MOAs by targeting important cancer survival-associated oncogenic proteins and/or by bypassing various treatment-resistant mechanisms. We then present a comprehensive review of the most advanced CPT analogues in clinical development, with the goal of resolving why no new CPTs have been FDA approved for cancer treatment, beyond irinotecan and topotecan. We argue that new CPT Top1 inhibitor drugs are unlikely being found to be significantly better than irinotecan and/or topotecan in terms of the overall antitumor activity and toxicity. The significance of CPT analogues that possess novel MOAs has not been sufficiently recognized so far. In our opinion, this is a research area with great potential to make a breakthrough for development of the next generation of CPT analogues that possess high efficacy (due to novel targets) and low toxicity (due to low inhibition of Top1 activity/function) for effective treatment of human disease, including cancer.
Indexed as
Identifiers
29312794PMC5752681W2982223252What 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.