ArticleCancers2023
SMAC Mimetics Synergistically Cooperate with HDAC Inhibitors Enhancing TNF-α Autocrine Signaling.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed, 3 citations in OpenAlex.
- Birinapant enhances cisplatin sensitivity in epithelial ovarian cancer through modulation of apoptotic and survival signaling pathways.Cancer chemotherapy and pharmacology · 2026Article
- Macrophage polarization regulated by the βTrCP-NF-κB inflammatory signaling pathway is required for valproic acid's dual role in breast tumor radiosensitivity and normal tissue radioprotection.Frontiers in immunology · 2026Article
- SMAC/DIABLO: A Guardian Angel in Boosting Anticancer Drug-Induced Apoptosis.Current molecular medicine · 2026Review
- Transcriptional remodeling shapes therapeutic vulnerability to necroptosis in acute lymphoblastic leukemia.Blood · 2025Article
- Epigenetic HDAC5 Inhibitor Reverses Craniofacial Neuropathic Pain in Mice.The journal of pain · 2024Article
- Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure.Viruses · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The overexpression of inhibitor of apoptosis (IAP) proteins is strongly related to poor survival of women with ovarian cancer. Recurrent ovarian cancers resist apoptosis due to the dysregulation of IAP proteins. Mechanistically, Second Mitochondrial Activator of Caspases (SMAC) mimetics suppress the functions of IAP proteins to restore apoptotic pathways resulting in tumor death. We previously conducted a phase 2 clinical trial of the single-agent SMAC mimetic birinapant and observed minimal drug response in women with recurrent ovarian cancer despite demonstrating on-target activity. Accordingly, we performed a high-throughput screening matrix to identify synergistic drug combinations with birinapant. SMAC mimetics in combination with an HDAC inhibitor showed remarkable synergy and was, therefore, selected for further evaluation. We show here that this synergy observed both in vitro and in vivo results from multiple convergent pathways to include increased caspase activation, HDAC inhibitor-mediated TNF-α upregulation, and alternative NF-kB signaling. These findings provide a rationale for the integration of SMAC mimetics and HDAC inhibitors in clinical trials for recurrent ovarian cancer where treatment options are still limited.
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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.