ArticleProceedings of the National Academy of Sciences of the United States of America2007
Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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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.
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Who cites it
132 citing papers in PubMed, 288 citations in OpenAlex.
- Prime, trap, and fail: engineering chromatin to potentiate topoisomerase II poisons in prostate cancer.Translational andrology and urology · 2026Article
- TOP2 and NOS2 Orchestrate the Generation of DNA Breaks to Promote Colitis Cancer Initiation.Cancers · 2026Article
- PDS5A and TOP2B cooperate for chromatin recruitment via CTCF.bioRxiv : the preprint server for biology · 2026Article
- NSC777201 exhibits anticancer activity against colorectal cancer cells by inducing multiple types of cell death.Cancer cell international · 2025Article
- Inclusion of JNK-independent drugs within multiagent chemotherapy improves response in relapsed high-risk neuroblastoma.Science advances · 2025Article
- Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans.GeroScience · 2025Article
- Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.Science advances · 2025Article
- Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Human Topoisomerase IIα Promotes Chromatin Condensation Via a Phase Transition.bioRxiv : the preprint server for biology · 2024Article
- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients.Molecular cancer · 2024Article
- Myeloperoxidase inhibition protects bone marrow mononuclear cells from DNA damage induced by the TOP2 poison anti-cancer drug etoposide.FEBS open bio · 2024Article
- Bioinformatic Analysis of Topoisomerase IIα Reveals Interdomain Interdependencies and Critical C-Terminal Domain Residues.International journal of molecular sciences · 2024Article
- MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.Cell death & disease · 2024Article
- Pharmacogenomics and Big Data in medical oncology: developments and challenges.Therapeutic advances in medical oncology · 2024Review
- A Route for Investigating Psoriasis: From the Perspective of the Pathological Mechanisms and Therapeutic Strategies of Cancer.International journal of molecular sciences · 2023Review
- DNA-PK inhibition extends the therapeutic effects of Top2 poisoning to non-proliferating cells, increasing activity at a cost.Scientific reports · 2023Article
- Naturally mutagenic sequence diversity in a human type II topoisomerase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.International journal of molecular sciences · 2023Review
- Prevalence of pathogenic variants in cancer-predisposing genes in second cancer after childhood solid cancers.Cancer medicine · 2023Article
72 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
7 authors at 1 institution in 1 country.
Funding
Abstract
Drugs that target DNA topoisomerase II (Top2), including etoposide (VP-16), doxorubicin, and mitoxantrone, are among the most effective anticancer drugs in clinical use. However, Top2-based chemotherapy has been associated with higher incidences of secondary malignancies, notably the development of acute myeloid leukemia in VP-16-treated patients. This association is suggestive of a link between carcinogenesis and Top2-mediated DNA damage. We show here that VP-16-induced carcinogenesis involves mainly the beta rather than the alpha isozyme of Top2. In a mouse skin carcinogenesis model, the incidence of VP-16-induced melanomas in the skin of 7,12-dimethylbenz[a]anthracene-treated mice is found to be significantly higher in TOP2beta(+) than in skin-specific top2beta-knockout mice. Furthermore, VP-16-induced DNA sequence rearrangements and double-strand breaks (DSBs) are found to be Top2beta-dependent and preventable by cotreatment with a proteasome inhibitor, suggesting the importance of proteasomal degradation of the Top2beta-DNA cleavage complexes in VP-16-induced DNA sequence rearrangements. VP-16 cytotoxicity in transformed cells expressing both Top2 isozymes is, however, found to be primarily Top2alpha-dependent. These results point to the importance of developing Top2alpha-specific anticancer drugs for effective chemotherapy without the development of treatment-related secondary malignancies.
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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.