ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Evaluation of Pharmacodynamic Responses to Cancer Therapeutic Agents Using DNA Damage Markers.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01989546 (Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations), which is not on this map. Cited by 24 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.
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations
Who cites it
24 citing papers in PubMed, 29 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
- Pharmacodynamic effects of the PARP inhibitor talazoparib (MDV3800, BMN 673) in patients with BRCA-mutated advanced solid tumors.Cancer chemotherapy and pharmacology · 2024Trial
- 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
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Phase I trial of the combination of bortezomib and clofarabine in adults with refractory tumors.Cancer chemotherapy and pharmacology · 2026Article
- Article
- A phase 1 study of orally administered 5-fluoro-2'-deoxycytidine with tetrahydrouridine in patients with refractory solid tumors.Cancer chemotherapy and pharmacology · 2025Article
- Article
- Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors.JCO precision oncology · 2025Article
- A Phase I Study of Nilotinib in Combination with Paclitaxel in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas.Cancer chemotherapy and pharmacology · 2025Article
- Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis.Cancer biology & therapy · 2022Article
- 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
- Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral-Framework Nucleic-Acid Nanostructures Functionalized with Osteogenic Growth Peptide.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- ROADMAPS: An Online Database of Response Data, Dosing Regimens, and Toxicities of Approved Oncology Drugs as Single Agents to Guide Preclinical In Vivo Studies.Cancer research · 2022Article
- Multiplexed-Based Assessment of DNA Damage Response to Chemotherapies Using Cell Imaging Cytometry.International journal of molecular sciences · 2022Article
- PARP Inhibitor Applicability: Detailed Assays for Homologous Recombination Repair Pathway Components.OncoTargets and therapy · 2022Review
- 5-Aza-4'-thio-2'-deoxycytidine, a New Orally Bioavailable Nontoxic "Best-in-Class": DNA Methyltransferase 1-Depleting Agent in Clinical Development.The Journal of pharmacology and experimental therapeutics · 2021Review
- Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies.Cancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeWe sought to examine the pharmacodynamic activation of the DNA damage response (DDR) pathway in tumors following anticancer treatment for confirmation of target engagement. EXPERIMENTAL
designWe evaluated the time course and spatial activation of 3 protein biomarkers of DNA damage recognition and repair (γH2AX, pS343-Nbs1, and Rad51) simultaneously in a quantitative multiplex immunofluorescence assay (IFA) to assess DDR pathway activation in tumor tissues following exposure to DNA-damaging agents.
resultsBecause of inherent biological variability, baseline DDR biomarker levels were evaluated in a colorectal cancer microarray to establish clinically relevant thresholds for pharmacodynamic activation. Xenograft-bearing mice and clinical colorectal tumor biopsies obtained from subjects exposed to DNA-damaging therapeutic regimens demonstrated marked intratumor heterogeneity in the timing and extent of DDR biomarker activation due, in part, to the cell-cycle dependency of DNA damage biomarker expression.
conclusionsWe have demonstrated the clinical utility of this DDR multiplex IFA in preclinical models and clinical specimens following exposure to multiple classes of cytotoxic agents, DNA repair protein inhibitors, and molecularly targeted agents, in both homologous recombination-proficient and -deficient contexts. Levels exceeding 4% nuclear area positive (NAP) γH2AX, 4% NAP pS343-Nbs1, and 5% cells with ≥5 Rad51 nuclear foci indicate a DDR activation response to treatment in human colorectal cancer tissue. Determination of effect-level cutoffs allows for robust interpretation of biomarkers with significant interpatient and intratumor heterogeneity; simultaneous assessment of biomarkers induced at different phases of the DDR guards against the risk of false negatives due to an ill-timed biopsy.
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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.