ReviewTranslational oncology2021
Etoposide, an anticancer drug involved in therapy-related secondary leukemia: Enzymes at play.
Review in Translational oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- The Effects of Podophyllotoxin Derivatives on Noncancerous Diseases: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- A randomized comparison of etoposide and cyclophosphamide for stem cell mobilization in newly diagnosed multiple myeloma.Scientific reports · 2026Trial
- Etoposide as Late-Line Therapy for Metastatic Extramammary Paget's Disease: A Case Series.The Journal of dermatology · 2026Article
- TargetPrior: a miRNA-signature embedded evolutionary learning framework for prioritizing drug targets in acute myeloid leukemia.Bioinformatics (Oxford, England) · 2026Article
- Chemotherapy resistance and risk stratification in gestational trophoblastic neoplasia: A systematic review and network meta-analysis.Acta obstetricia et gynecologica Scandinavica · 2026Review
- Fluorophenylalanine-Containing Dipeptides with Antibiofilm Activity AgainstMolecules (Basel, Switzerland) · 2026Article
- A Critical Analysis of the Impact of Etoposide as a Topoisomerase II Inhibitor in Cervical Cancer Treatment: A Review.Cancer medicine · 2026Review
- ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks.Nature communications · 2026Article
- Design and application of a TiOEnvironmental science and pollution research international · 2026Article
- Review
- Alkaloids mediated regulation of microRNA in cancer: molecular insights and emerging therapeutic strategies.Frontiers in oncology · 2026Review
- Unveiling the role of UGT enzymes in chemoresistance: a path to enhanced cancer pharmacotherapy.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Reply to: The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells.medRxiv : the preprint server for health sciences · 2025Article
- Therapy-related acute myeloid leukemia following aggressive treatment for pediatric medulloblastoma: a case report of a 13-year-old and review of literature.Annals of medicine and surgery (2012) · 2025Article
- Carnitine Shuttle and Ferroptosis in Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Direct functional HOXA9/DNA-binding competitors versus epigenetic inhibitors of HOXA9 expression on cell proliferation, death and differentiation processes in the model of MLL-rearranged acute myeloid leukemia.Investigational new drugs · 2025Article
- Article
- The long-term effects of chemotherapy on normal blood cells.Nature genetics · 2025Article
- Identification of novel genetic mutations for the treatment prognostication of canine lymphoma.NPJ precision oncology · 2025Article
- Purinergic Receptor P2Y2 Activity Prevents DNA Damage in CClJournal of cellular biochemistry · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Etoposide is a semi-synthetic glycoside derivative of podophyllotoxin, also known as VP-16. It is a widely used anticancer medicine in clinics. Unfortunately, high doses or long-term etoposide treatment can induce therapy-related leukemia. The mechanism by which etoposide induces secondary hematopoietic malignancies is still unclear. In this article, we review the potential mechanisms of etoposide induced therapy-related leukemia. Etoposide related leukemogenesis is known to depend on reactive oxidative metabolites of etoposide, notably etoposide quinone, which interacts with cellular proteins such as topoisomerases II (TOP2), CREB-binding protein (CREBBP), and T-Cell Protein Tyrosine Phosphatase (TCPTP). CYP3A4 and CYP3A5 metabolize etoposide to etoposide catechol, which readily oxidizes to etoposide quinone. As a poison of TOP2 enzymes, etoposide and its metabolites induce DNA double-stranded breaks (DSB), and the accumulation of DSB triggers cell apoptosis. If the cell survives, the DSB gives rise to the likelihood of faulty DNA repair events. The gene translocation could occur in mixed-lineage leukemia (MLL) gene, which is well-known in leukemogenesis. Recently, studies have revealed that etoposide metabolites, especially etoposide quinone, can covalently bind to cysteines residues of CREBBP and TCPTP enzymes, . This leads to enzyme inhibition and further affects histone acetylation and phosphorylation of the JAK-STAT pathway, thus putatively altering the proliferation and differentiation of hematopoietic stem cells (HSC). In brief, current studies suggest that etoposide and its metabolites contribute to etoposide therapy-related leukemia through TOP2 mediated DSB and impairs specific enzyme activity, such as CREBBP and TCPTP.
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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.