ArticleNature biotechnology2014
Smac mimetics and innate immune stimuli synergize to promote tumor death.
Article in Nature biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 132 citations in OpenAlex.
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- Apoptotic modulators enhance oncolytic virus-induced cytokine killing in acute myeloid leukaemia (AML).British journal of cancer · 2026Article
- Hematopoietic expression of cIAP2 drives inflammation and heart failure after myocardial infarction.Nature cardiovascular research · 2026Article
- Targeting leucine-rich repeat kinase 2 overcomes resistance to oncolytic herpes simplex virus-based therapies in glioblastoma.Nature communications · 2026Article
- Second Mitochondrial Activator of Caspases Mimetics Accelerate Progression of Locally Advanced Head and Neck Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models.Cell reports. Medicine · 2025Article
- The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection.Science translational medicine · 2025Article
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Xevinapant plus avelumab in advanced solid tumours, with a dose expansion in advanced non-small-cell lung cancer: exploratory biomarker, safety and efficacy analyses from an open-label, nonrandomised phase Ib study.Therapeutic advances in medical oncology · 2025Article
- SMAC mimetics sensitize HIV-infected cells to oncolytic virus-mediated death.Frontiers in immunology · 2025Article
- Lung epithelial and alveolar macrophage-like cell interactions significantly modify innate responses to bacterial endotoxin with the involvement of direct cellular contacts, TNF-α, ICAM1 and MCP-1.Frontiers in immunology · 2025Article
- 3D Tumor Model to Study Immune Cell Infiltration.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds.Cell death & disease · 2024Article
- Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.Nature reviews. Cancer · 2024Review
- Cancer cell-specific and pro-apoptotic SMAC peptide-doxorubicin conjugated prodrug encapsulated aposomes for synergistic cancer immunotherapy.Journal of nanobiotechnology · 2024Article
- Tumor microenvironment mimicking 3D models unveil the multifaceted effects of SMAC mimetics.iScience · 2023Article
- Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells.Frontiers in pharmacology · 2023Article
- A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.Cancers · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma.Blood advances · 2021Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Smac mimetic compounds (SMC), a class of drugs that sensitize cells to apoptosis by counteracting the activity of inhibitor of apoptosis (IAP) proteins, have proven safe in phase 1 clinical trials in cancer patients. However, because SMCs act by enabling transduction of pro-apoptotic signals, SMC monotherapy may be efficacious only in the subset of patients whose tumors produce large quantities of death-inducing proteins such as inflammatory cytokines. Therefore, we reasoned that SMCs would synergize with agents that stimulate a potent yet safe "cytokine storm." Here we show that oncolytic viruses and adjuvants such as poly(I:C) and CpG induce bystander death of cancer cells treated with SMCs that is mediated by interferon beta (IFN-β), tumor necrosis factor alpha (TNF-α) and/or TNF-related apoptosis-inducing ligand (TRAIL). This combinatorial treatment resulted in tumor regression and extended survival in two mouse models of cancer. As these and other adjuvants have been proven safe in clinical trials, it may be worthwhile to explore their clinical efficacy in combination with SMCs.
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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.