ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
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- Phase I trial of the combination of bortezomib and clofarabine in adults with refractory tumors.Cancer chemotherapy and pharmacology · 2026Article
- Potent ferroptosis agent RSL3 induces cleavage of Pyroptosis-Specific gasdermins in Cancer cells.Scientific reports · 2025Article
- Optimization of 1,2,4-Triazole-Based p97 Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2023Article
- Interrupting specific hydrogen bonds between ELF3 and MED23 as an alternative drug resistance-free strategy for HER2-overexpressing cancers.Journal of advanced research · 2023Article
- Comparative Oncology Assessment of a Novel Inhibitor of Valosin-Containing Protein in Tumor-Bearing Dogs.Molecular cancer therapeutics · 2022Article
- Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis.Molecular cancer therapeutics · 2021Article
- Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD.Frontiers in medicine · 2021Review
- Targeting triple-negative breast cancers with the Smac-mimetic birinapant.Cell death and differentiation · 2020Article
- Prioritization of novel ADPKD drug candidates from disease-stage specific gene expression profiles.EBioMedicine · 2020Article
- Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox.Cancers · 2019Review
- What Can Be Done to Improve Research Biopsy Quality in Oncology Clinical Trials?Journal of oncology practice · 2018Article
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- The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity.Cancer research · 2017Article
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- Translating pharmacodynamic biomarkers from bench to bedside: analytical validation and fit-for-purpose studies to qualify multiplex immunofluorescent assays for use on clinical core biopsy specimens.Seminars in oncology · 2016Review
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Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeTo support clinical pharmacodynamic evaluation of the Smac mimetic TL32711 (birinapant) and other apoptosis-targeting drugs, we describe the development, validation, and application of novel immunoassays for 15 cytosolic and membrane-associated proteins indicative of the induction, onset, and commitment to apoptosis in human tumors. EXPERIMENTAL
designThe multiplex immunoassays were constructed on the Luminex platform with apoptosis biomarkers grouped into three panels. Panel 1 contains Bak, Bax, total caspase-3, total lamin-B (intact and 45 kDa fragment), and Smac; panel 2 contains Bad, Bax-Bcl-2 heterodimer, Bcl-xL, Bim, and Mcl1; and panel 3 contains active (cleaved) caspase-3, Bcl-xL-Bak heterodimer, Mcl1-Bak heterodimer, pS99-Bad, and survivin. Antibody specificity was confirmed by immunoprecipitation and Western blot analysis.
resultsTwo laboratories analytically validated the multiplex immunoassays for application with core-needle biopsy samples processed to control preanalytical variables; the biologic variability for each biomarker was estimated from xenograft measurements. Studies of TL32711 in xenograft models confirmed a dose-dependent increase in activated caspase-3 6 hours after dosing and provided assay fit-for-purpose confirmation. Coincident changes in cytosolic lamin-B and subsequent changes in Bcl-xL provided correlative evidence of caspase-3 activation. The validated assay is suitable for use with clinical specimens; 14 of 15 biomarkers were quantifiable in patient core-needle biopsies.
conclusionsThe validated multiplex immunoassays developed for this study provided proof of mechanism data for TL32711 and are suitable for quantifying apoptotic biomarkers in clinical trials.
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