ArticleCell death & disease2013
Smac mimetics induce inflammation and necrotic tumour cell death by modulating macrophage activity.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 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
- The reprogramming impact of SMAC-mimetic on glioblastoma stem cells and the immune tumor microenvironment evolution.Journal of experimental & clinical cancer research : CR · 2025Article
- HTRA2/OMI-Mediated Mitochondrial Quality Control Alters Macrophage Polarization Affecting Systemic Chronic Inflammation.International journal of molecular sciences · 2024Review
- Mitochondrial control of inflammation.Nature reviews. Immunology · 2023Review
- The resurrection of RIP kinase 1 as an early cell death checkpoint regulator-a potential target for therapy in the necroptosis era.Experimental & molecular medicine · 2022Review
- A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.Cancers · 2022Review
- The Smac mimetic BV6 cooperates with STING to induce necroptosis in apoptosis-resistant pancreatic carcinoma cells.Cell death & disease · 2021Article
- Therapeutics Targeting the Core Apoptotic Machinery.Cancers · 2021Review
- Loss of cIAP1 in Endothelial Cells Limits Metastatic Extravasation through Tumor-Derived Lymphotoxin Alpha.Cancers · 2021Article
- Structure-based identification of a new IAP-targeting compound that induces cancer cell death inducing NF-κB pathway.Computational and structural biotechnology journal · 2021Article
- In vitro analysis reveals necroptotic signaling does not provoke DNA damage or HPRT mutations.Cell death & disease · 2020Article
- Emerging neo adjuvants for harnessing therapeutic potential of M1 tumor associated macrophages (TAM) against solid tumors: Enusage of plasticity.Annals of translational medicine · 2020Review
- The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy.Cells · 2020Review
- LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness.Frontiers in oncology · 2020Review
- Article
- The Mitochondrion as an Emerging Therapeutic Target in Cancer.Trends in molecular medicine · 2020Review
- Inhibitor of apoptosis proteins are potential targets for treatment of granulosa cell tumors - implications from studies in KGN.Journal of ovarian research · 2019Article
- HTiP: High-Throughput Immunomodulator Phenotypic Screening Platform to Reveal IAP Antagonists as Anti-cancer Immune Enhancers.Cell chemical biology · 2019Article
- Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment.Computational and structural biotechnology journal · 2019Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Smac mimetics (SMs) comprise a class of small molecules that target members of the inhibitor of apoptosis family of pro-survival proteins, whose expression in cancer cells hinders the action of conventional chemotherapeutics. Herein, we describe the activity of SM83, a newly synthesised dimeric SM, in two cancer ascites models: athymic nude mice injected intraperitoneally with IGROV-1 human ovarian carcinoma cells and immunocompetent BALB/c mice injected with murine Meth A sarcoma cells. SM83 rapidly killed ascitic IGROV-1 and Meth A cells in vivo (prolonging mouse survival), but was ineffective against the same cells in vitro. IGROV-1 cells in nude mice were killed within the ascites by a non-apoptotic, tumour necrosis factor (TNF)-dependent mechanism. SM83 administration triggered a rapid inflammatory event characterised by host secretion of TNF, interleukin-1β and interferon-γ. This inflammatory response was associated with the reversion of the phenotype of tumour-associated macrophages from a pro-tumoural M2- to a pro-inflammatory M1-like state. SM83 treatment was also associated with a massive recruitment of neutrophils that, however, was not essential for the antitumoural activity of this compound. In BALB/c mice bearing Meth A ascites, SM83 treatment was in some cases curative, and these mice became resistant to a second injection of cancer cells, suggesting that they had developed an adaptive immune response. Altogether, these results indicate that, in vivo, SM83 modulates the immune system within the tumour microenvironment and, through its pro-inflammatory action, leads cancer cells to die by necrosis with the release of high-mobility group box-1. In conclusion, our work provides evidence that SMs could be more therapeutically active than expected by stimulating the immune system.
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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.