ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Monitoring drug-induced gammaH2AX as a pharmacodynamic biomarker in individual circulating tumor cells.
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 NCT02407327 (Trattamento Personalizzato Del Tumore NSCLC Avanzato), which is not on this map. Cited by 57 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.
Trattamento Personalizzato Del Tumore NSCLC Avanzato: Potenziali Applicazioni Della Caratterizzazione Fenotipica e Molecolare Delle Cellule Tumorali Circolanti (CTC)
Who cites it
57 citing papers in PubMed, 95 citations in OpenAlex.
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- Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer.Investigational new drugs · 2016Trial
- Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology.Breast cancer research and treatment · 2011Trial
- Mass cytometric detection of homologous recombination proficiency in circulating tumor cells to predict chemoresistance of metastatic breast cancer patients.International journal of cancer · 2025Article
- Quantification of Unencapsulated Drug in Target Tissues Demonstrates Pharmacological Properties and Therapeutic Effects of Liposomal Topotecan (FF-10850).Pharmaceutical research · 2024Article
- A multiparameter liquid biopsy approach allows to track melanoma dynamics and identify early treatment resistance.NPJ precision oncology · 2024Article
- Article
- Circulating Tumor Cells in Breast Cancer Patients: A Balancing Act between Stemness, EMT Features and DNA Damage Responses.Cancers · 2022Review
- A phase I study of veliparib with cyclophosphamide and veliparib combined with doxorubicin and cyclophosphamide in advanced malignancies.Cancer chemotherapy and pharmacology · 2022Article
- Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status.Cells · 2021Article
- KAT8/MOF-Mediated Anti-Cancer Mechanism of Gemcitabine in Human Bladder Cancer Cells.Biomolecules & therapeutics · 2021Article
- Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability.Cells · 2021Review
- Monitoring DNA Damage and Repair in Peripheral Blood Mononuclear Cells of Lung Cancer Radiotherapy Patients.Cancers · 2020Article
- Drug Design Targeting T-Cell Factor-Driven Epithelial-Mesenchymal Transition as a Therapeutic Strategy for Colorectal Cancer.Journal of medicinal chemistry · 2019Article
- Spontaneous γH2AX foci in human dermal fibroblasts in relation to proliferation activity and aging.Aging · 2019Article
- Recent advances in microfluidic methods in cancer liquid biopsy.Biomicrofluidics · 2019Review
- 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
- The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity.Cancer research · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
purposeCirculating tumor cells (CTC) in peripheral blood of patients potentially represent a fraction of solid tumor cells available for more frequent pharmacodynamic assessment of drug action than is possible using tumor biopsy. However, currently available CTC assays are limited to cell membrane antigens. Here, we describe an assay that directly examines changes in levels of the nuclear DNA damage marker gammaH2AX in individual CTCs of patients treated with chemotherapeutic agents. EXPERIMENTAL
designAn Alexa Fluor 488-conjugated monoclonal gammaH2AX antibody and epithelial cancer cell lines treated with topotecan and spiked into whole blood were used to measure DNA damage-dependent nuclear gammaH2AX signals in individual CTCs. Time-course changes in both CTC number and gammaH2AX levels in CTCs were also evaluated in blood samples from patients undergoing treatment.
resultsThe percentage of gammaH2AX-positive CTCs increased in a concentration-dependent manner in cells treated with therapeutically relevant concentrations of topotecan ex vivo. In samples from five patients, percent gammaH2AX-positive cells increased post-treatment from a mean of 2% at baseline (range, 0-6%) to a mean of 38% (range, 22-64%) after a single day of drug administration; this increase was irrespective of increases or decreases in the total CTC count.
conclusionsThese data show promise for monitoring dynamic changes in nuclear biomarkers in CTCs (in addition to CTC count) for rapidly assessing drug activity in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research.
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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.