ArticleInternational journal of cancer2011
A microdosing approach for characterizing formation and repair of carboplatin-DNA monoadducts and chemoresistance.
Article in International journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Optimizing local control in the surgical management of bladder cancer.Nature reviews. Urology · 2026Review
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- Liquid Chromatography-Mass Spectrometry Screening of Cyclophosphamide DNA Damage In Vitro and in Patients Undergoing Chemotherapy Treatment.Chemical research in toxicology · 2023Article
- HPLC-Parallel accelerator and molecular mass spectrometry analysis ofJournal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- Strategic, feasibility, economic, and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?Clinical and translational science · 2022Review
- Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients.BMC veterinary research · 2021Article
- Preclinical Models for Bladder Cancer Research.Hematology/oncology clinics of North America · 2021Review
- Phase 0/microdosing approaches: time for mainstream application in drug development?Nature reviews. Drug discovery · 2020Review
- Oxaliplatin-DNA Adducts as Predictive Biomarkers of FOLFOX Response in Colorectal Cancer: A Potential Treatment Optimization Strategy.Molecular cancer therapeutics · 2020Article
- Radiocarbon Tracers in Toxicology and Medicine: Recent Advances in Technology and Science.Toxics · 2019Review
- Correlation of Platinum Cytotoxicity to Drug-DNA Adduct Levels in a Breast Cancer Cell Line Panel.Chemical research in toxicology · 2018Article
- COX-2/sEH Dual Inhibitor PTUPB Potentiates the Antitumor Efficacy of Cisplatin.Molecular cancer therapeutics · 2018Article
- Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing.Clinical and translational science · 2017Review
- A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer.International journal of cancer · 2017Article
- Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.Molecular cancer therapeutics · 2017Article
- DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine.Chemical research in toxicology · 2017Article
- A SPATIOTEMPORAL MODEL TO SIMULATE CHEMOTHERAPY REGIMENS FOR HETEROGENEOUS BLADDER CANCER METASTASES TO THE LUNG.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2017Article
- Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.Chemical research in toxicology · 2016Review
- Diagnostic Microdosing Approach to Study Gemcitabine Resistance.Chemical research in toxicology · 2016Article
- Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development.Clinical and translational science · 2016Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Formation and repair of platinum (Pt)-induced DNA adducts is a critical step in Pt drug-mediated cytotoxicity. Measurement of Pt-DNA adduct kinetics in tumors may be useful for better understanding chemoresistance and therapeutic response. However, this concept has yet to be rigorously tested because of technical challenges in measuring the adducts at low concentrations and consistent access to sufficient tumor biopsy material. Ultrasensitive accelerator mass spectrometry was used to detect [(14)C]carboplatin-DNA monoadducts at the attomole level, which are the precursors to Pt-DNA crosslink formation, in six cancer cell lines as a proof-of-concept. The most resistant cells had the lowest monoadduct levels at all time points over 24 hr. [(14)C]Carboplatin "microdoses" (1/100th the pharmacologically effective concentration) had nearly identical adduct formation and repair kinetics compared to therapeutically relevant doses, suggesting that the microdosing approach can potentially be used to determine the pharmacological effects of therapeutic treatment. Some of the possible chemoresistance mechanisms were also studied, such as drug uptake/efflux, intracellular inactivation and DNA repair in selected cell lines. Intracellular inactivation and efficient DNA repair each contributed significantly to the suppression of DNA monoadduct formation in the most resistant cell line compared to the most sensitive cell line studied (p < 0.001). Nucleotide excision repair (NER)-deficient and -proficient cells showed substantial differences in carboplatin monoadduct concentrations over 24 hr that likely contributed to chemoresistance. The data support the utility of carboplatin microdosing as a translatable approach for defining carboplatin-DNA monoadduct formation and repair, possibly by NER, which may be useful for characterizing chemoresistance in vivo.
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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.