ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Development of a validated immunofluorescence assay for γH2AX as a pharmacodynamic marker of topoisomerase I inhibitor activity.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01851369 (A Phase I/II Trial of TRC102), which is not on this map. Cited by 46 papers.
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.
A Phase I/II Trial of TRC102 (Methoxyamine HCl) in Combination With Temozolomide in Patients With Relapsed Solid Tumors and Lymphomas
Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- NCI 10211: a phase II, single-arm study of berzosertib in combination with irinotecan in patients with advanced TP53 mutant gastroesophageal cancer.The oncologist · 2025Trial
- Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia.Leukemia research · 2017Trial
- Perspectives From an Expert-Guided Discussion on Maximizing the Research Potential of Small Biopsy Tissue.JCO precision oncology · 2026Article
- Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.Current issues in molecular biology · 2026Review
- Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas.Cancer chemotherapy and pharmacology · 2025Article
- Mouse pancreatic tumor organoids reveal synergistic efficacy of low-dose anticancer drug and radiation combinations.Frontiers in medicine · 2025Article
- Profiling DNA damage in 3D Histology Samples.Medical optical imaging and virtual microscopy image analysis : first International Workshop, MOVI 2022, held in conjunction with MICCAI 2022, Singapore, September 18, 2022, Proceedings. MOVI (Workshop) (1st : 2022 : Singapore) · 2022Article
- The Potential of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates.Pharmaceutics · 2022Review
- A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas.Frontiers in oncology · 2022Article
- Article
- The Indenoisoquinoline TOP1 Inhibitors Selectively Target Homologous Recombination-Deficient and Schlafen 11-Positive Cancer Cells and Synergize with Olaparib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Evaluation of Pharmacodynamic Responses to Cancer Therapeutic Agents Using DNA Damage Markers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- NCI Comparative Oncology Program Testing of Non-Camptothecin Indenoisoquinoline Topoisomerase I Inhibitors in Naturally Occurring Canine Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- What Can Be Done to Improve Research Biopsy Quality in Oncology Clinical Trials?Journal of oncology practice · 2018Article
- Novel Fluoroindenoisoquinoline Non-Camptothecin Topoisomerase I Inhibitors.Molecular cancer therapeutics · 2018Article
- Article
- Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormantMolecular autism · 2018Article
- The contribution of DNA replication stress marked by high-intensity, pan-nuclear γH2AX staining to chemosensitization by CHK1 and WEE1 inhibitors.Cell cycle (Georgetown, Tex.) · 2018Article
- Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay.PloS one · 2017Article
- STA-8666, a novel HSP90 inhibitor/SN-38 drug conjugate, causes complete tumor regression in preclinical mouse models of pediatric sarcoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
purposePhosphorylated histone H2AX (γH2AX) serves as a biomarker for formation of DNA double-strand break repair complexes. A quantitative pharmacodynamic immunofluorescence assay for γH2AX was developed, validated, and tested in human tumor xenograft models with the use of clinically relevant procedures. EXPERIMENTAL
designThe γH2AX immunofluorescence assay uses a novel data quantitation and image processing algorithm to determine the extent of nuclear-specific γH2AX staining in tumor needle biopsies and hair follicles collected from mice bearing topotecan-responsive A375 xenografts. After method validation with the topoisomerase I (Top1) inhibitor topotecan, the assay was used to compare pharmacodynamic properties of three structurally related indenoisoquinoline Top1 inhibitors.
resultsγH2AX response to topotecan was quantified over a 60-fold dose range (0.016-1.0 times the murine single-dose maximum tolerated dose), and significant pharmacodynamic response was measured at the mouse equivalent of the 1.5 mg/m(2) clinical dose as well as the lowest dose tested. Responses were within a time window amenable for biopsy collection in clinical trials. These studies enabled characterization of dose and time responses for three indenoisoquinolines, resulting in selection of two for clinical evaluation. γH2AX response to Top1 inhibitors in hair follicles was also observable above a minimal dose threshold.
conclusionsOur γH2AX assay is sufficiently accurate and sensitive to quantify γH2AX in tumor samples and will be used in correlative studies of two indenoisoquinolines in a phase I clinical trial at the National Cancer Institute. Data suggest that hair follicles may potentially serve as a surrogate tissue to evaluate tumor γH2AX response to Top1 inhibitors.
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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.