ArticleCell death and differentiation2018
Simulating and predicting cellular and in vivo responses of colon cancer to combined treatment with chemotherapy and IAP antagonist Birinapant/TL32711.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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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.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins.Cell death and differentiation · 2026Article
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- Tumor‑stroma ratio as a clinical prognostic factor in colorectal carcinoma: A meta‑analysis of 7,934 patients.Oncology letters · 2025Article
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Combination of bazedoxifene with chemotherapy and SMAC-mimetics for the treatment of colorectal cancer.Cell death & disease · 2024Article
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Tumor-intrinsic and immune modulatory roles of receptor-interacting protein kinases.Trends in biochemical sciences · 2022Review
- Systems Biology in ELIXIR: modelling in the spotlight.F1000Research · 2022Article
- Therapeutics Targeting the Core Apoptotic Machinery.Cancers · 2021Review
- Molecular subtype-specific responses of colon cancer cells to the SMAC mimetic Birinapant.Cell death & disease · 2020Article
- Convergence of pathway analysis and pattern recognition predicts sensitization to latest generation TRAIL therapeutics by IAP antagonism.Cell death and differentiation · 2020Article
- Circular RNA circFBXO11 modulates hepatocellular carcinoma progress and oxaliplatin resistance through miR-605/FOXO3/ABCB1 axis.Journal of cellular and molecular medicine · 2020Article
- Hepatitis B virus upregulates cellular inhibitor of apoptosis protein 2 expression via the PI3K/AKT/NF-κB signaling pathway in liver cancer.Oncology letters · 2020Article
- System-based approaches as prognostic tools for glioblastoma.BMC cancer · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Apoptosis resistance contributes to treatment failure in colorectal cancer (CRC). New treatments that reinstate apoptosis competency have potential to improve patient outcome but require predictive biomarkers to target them to responsive patient populations. Inhibitor of apoptosis proteins (IAPs) suppress apoptosis, contributing to drug resistance; IAP antagonists such as TL32711 have therefore been developed. We developed a systems biology approach for predicting response of CRC cells to chemotherapy and TL32711 combinations in vitro and in vivo. CRC cells responded poorly to TL32711 monotherapy in vitro; however, co-treatment with 5-fluorouracil (5-FU) and oxaliplatin enhanced TL32711-induced apoptosis. Notably, cells from genetically identical populations responded highly heterogeneously, with caspases being activated both upstream and downstream of mitochondrial outer membrane permeabilisation (MOMP). These data, combined with quantities of key apoptosis regulators were sufficient to replicate in vitro cell death profiles by mathematical modelling. In vivo, apoptosis protein expression was significantly altered, and mathematical modelling for these conditions predicted higher apoptosis resistance that could nevertheless be overcome by combination of chemotherapy and TL32711. Subsequent experimental observations agreed with these predictions, and the observed effects on tumour growth inhibition correlated robustly with apoptosis competency. We therefore obtained insights into intracellular signal transduction kinetics and their population-based heterogeneities for chemotherapy/TL32711 combinations and provide proof-of-concept that mathematical modelling of apoptosis competency can simulate and predict responsiveness in vivo. Being able to predict response to IAP antagonist-based treatments on the background of cell-to-cell heterogeneities in the future might assist in improving treatment stratification approaches for these emerging apoptosis-targeting agents.
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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.