Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (747 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside; Eposide; Vepesid; Etoposide, alpha-D-Glucopyranosyl Isomer; alpha-D-Glucopyranosyl Isomer Etoposide; Etoposide, alpha D Glucopyranosyl Isomer; Etoposide, (5S)-Isomer; Etoposide, (5a alpha)-Isomer.
Where it fits in the MeSH classification
- Broader topics
- Podophyllotoxin; Glucosides
Related concepts
- Podophyllotoxin
Research landscape
PubMed indexes 18,595 records tagged with the MeSH heading “Etoposide” (counts retrieved 2026-10-31). 1,969 of them (10.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 6,968 records.
Reviews account for 1,228 records (6.6%) and meta-analyses for 60. Randomized controlled trials number 1,246 (6.7%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 6,968 |
| 2000-2009 | 5,504 |
| 2010-2019 | 4,154 |
| 2020 onward | 1,969 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,228 | 6.6% |
| Meta-analyses | 60 | 0.3% |
| Randomized controlled trials | 1,246 | 6.7% |
Method: PubMed query "Etoposide"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
A systematic investigation of the maximum tolerated dose of cytotoxic chemotherapy with and without supportive care in mice [1]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundCytotoxic chemotherapeutics form the cornerstone of systemic treatment of many cancers.
- Closing excerpt
- ConclusionThese data form a resource for future studies using chemotherapy in mice, increasing comparability between studies, reducing the number of mice needed for dose optimisation experiments and potentially improving translation to the clinic.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (190 words)
BackgroundCytotoxic chemotherapeutics form the cornerstone of systemic treatment of many cancers. Patients are dosed at maximum tolerated dose (MTD), which is carefully determined in phase I studies. In contrast, in murine studies, dosages are often based on customary practice or small pilot studies, which often are not well documented. Consequently, research groups need to replicate experiments, resulting in an excess use of animals and highly variable dosages across the literature. In addition, while patients often receive supportive treatments in order to allow dose escalation, mice do not. These issues could affect experimental results and hence clinical translation.MethodsTo address this, we determined the single-dose MTD in BALB/c and C57BL/6 mice for a range of chemotherapeutics covering the canonical classes, with clinical score and weight as endpoints.ResultsWe found that there was some variation in MTDs between strains and the tolerability of repeated cycles of chemotherapy at MTD was drug-dependent. We also demonstrate that dexamethasone reduces chemotherapy-induced weight loss in mice.ConclusionThese data form a resource for future studies using chemotherapy in mice, increasing comparability between studies, reducing the number of mice needed for dose optimisation experiments and potentially improving translation to the clinic.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29037232 · DOI · PMC5644108
Drug-induced cell cycle modulation leading to cell-cycle arrest, nuclear mis-segregation, or endoreplication [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundCancer cell responses to chemotherapeutic agents vary, and this may reflect different defects in DNA repair, cell-cycle checkpoints, and apoptosis control.
- Closing excerpt
- This assay system will represent a powerful drug-discovery tool for the development of the next generation of anti-cancer therapies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (240 words)
BackgroundCancer cell responses to chemotherapeutic agents vary, and this may reflect different defects in DNA repair, cell-cycle checkpoints, and apoptosis control. Cytometry analysis only quantifies dye-incorporation to examine DNA content and does not reflect the biological complexity of the cell cycle in drug discovery screens.ResultsUsing population and time-lapse imaging analyses of cultured immortalized cells expressing a new version of the fluorescent cell-cycle indicator, Fucci (Fluorescent Ubiquitination-based Cell Cycle Indicator), we found great diversity in the cell-cycle alterations induced by two anticancer drugs. When treated with etoposide, an inhibitor of DNA topoisomerase II, HeLa and NMuMG cells halted at the G2/M checkpoint. HeLa cells remained there, but NMuMG cells then overrode the checkpoint and underwent nuclear mis-segregation or avoided the checkpoint and entered the endoreplication cycle in a drug concentration dependent manner. In contrast, an inhibitor of Cdk4 led to G1 arrest or endoreplication in NMuMG cells depending upon the initial cell-cycle phase of drug exposure.ConclusionsDrug-induced cell cycle modulation varied not only between different cell types or following treatment with different drugs, but also between cells treated with different concentrations of the same drug or following drug addition during different phases of the cell cycle. By combining cytometry analysis with the Fucci probe, we have developed a novel assay that fully integrates the complexity of cell cycle regulation into drug discovery screens. This assay system will represent a powerful drug-discovery tool for the development of the next generation of anti-cancer therapies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 21226962 · DOI · PMC3277280
Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin [3]
Abstract reading summary — source excerpts
- Opening excerpt
- New antibacterials are needed to tackle antibiotic-resistant bacteria.
- Closing excerpt
- Structure-based strategies for developing topo2A antibacterials are suggested.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide's antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a 'pair of swing-doors' hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1's bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 26640131 · DOI · PMC4686662
Downregulation of O-GlcNAcylation enhances etoposide-induced p53-mediated apoptosis in HepG2 human liver cancer cells [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Etoposide, an anticancer drug that inhibits topoisomerase II, is commonly used in combination chemotherapy.
- Closing excerpt
- These findings suggest that downregulating O-GlcNAcylation may enhance the efficacy of etoposide-based chemotherapy and help overcome tumor resistance.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (170 words)
Etoposide, an anticancer drug that inhibits topoisomerase II, is commonly used in combination chemotherapy. However, the impact of O-GlcNAcylation regulation on etoposide's anticancer effects has rarely been investigated. This study evaluated the effect of etoposide on cellular O-GlcNAcylation and whether modulating this process enhances etoposide-induced apoptosis. O-GlcNAc expression was measured after 24 h of etoposide treatment, and the effect of O-GlcNAc transferase (OGT) inhibition by OSMI-1 on etoposide's anticancer activity in HepG2 human liver cancer cells was quantitatively analyzed. Additionally, molecular analyses were used to confirm that the observed effects were mediated by p53-induced apoptosis. Etoposide reduced O-GlcNAcylation in a dose-dependent manner without directly interacting with OGT. Cotreatment with 20 μm of OSMI-1 lowered the IC50 value for cell viability by approximately 1.64-fold to 60.68 μm and increased the EC50 value for cytotoxicity by around 4.07-fold to 43.41 μm. Furthermore, this synergistic effect was linked to the activation of the p53/caspase-3/PARP1 pathway. These findings suggest that downregulating O-GlcNAcylation may enhance the efficacy of etoposide-based chemotherapy and help overcome tumor resistance.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40237201 · DOI · PMC12226413
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Etoposide: four decades of development of a topoisomerase II inhibitor [5]
- Research article Etoposide, topoisomerase II and cancer [6]
- Research article Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives [7]
- Research article Etoposide (VP-16-213). Current status of an active anticancer drug [8]
- Research article Mechanism of action of antitumor drug etoposide: a review [9]
- Research article Cellular response to etoposide treatment [10]
References
- Aston WJ, Hope DE, Nowak AK, Robinson BW, Lake RA, Lesterhuis WJ. A systematic investigation of the maximum tolerated dose of cytotoxic chemotherapy with and without supportive care in mice. . 2017. PMID 29037232 · DOI · PMC5644108
- Sakaue-Sawano A, Kobayashi T, Ohtawa K, Miyawaki A. Drug-induced cell cycle modulation leading to cell-cycle arrest, nuclear mis-segregation, or endoreplication. . 2011. PMID 21226962 · DOI · PMC3277280
- Chan PF, Srikannathasan V, Huang J, Cui H, Fosberry AP, Gu M, et al.. Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin. . 2015. PMID 26640131 · DOI · PMC4686662
- Lee J, Koo GB, Park J, Han BC, Kwon M, Lee SH. Downregulation of O-GlcNAcylation enhances etoposide-induced p53-mediated apoptosis in HepG2 human liver cancer cells. . 2025. PMID 40237201 · DOI · PMC12226413
- Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer. 1998. PMID 9893622 · DOI
- Baldwin EL, Osheroff N. Etoposide, topoisomerase II and cancer. Curr Med Chem Anticancer Agents. 2005. PMID 16101488 · DOI
- Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004. PMID 15302526 · DOI
- O'Dwyer PJ, Leyland-Jones B, Alonso MT, Marsoni S, Wittes RE. Etoposide (VP-16-213). Current status of an active anticancer drug. N Engl J Med. 1985. PMID 2983208 · DOI
- van Maanen JM, Retèl J, de Vries J, Pinedo HM. Mechanism of action of antitumor drug etoposide: a review. J Natl Cancer Inst. 1988. PMID 2848132 · DOI
- Montecucco A, Biamonti G. Cellular response to etoposide treatment. Cancer Lett. 2007. PMID 17166655 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.