ArticleOncotarget2016
Inhibitor of Apoptosis Proteins (IAPs) are commonly dysregulated in GIST and can be pharmacologically targeted to enhance the pro-apoptotic activity of imatinib.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- TheInternational journal of molecular sciences · 2021Trial
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors.Clinical and experimental medicine · 2025Review
- Exploring BIRC family genes as prognostic biomarkers and therapeutic targets in prostate cancer.Discover oncology · 2025Article
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Host Cell Death and Modulation of Immune Response againstInternational journal of molecular sciences · 2024Review
- Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis.Molecular cancer therapeutics · 2021Article
- Anti-tumoral activity of single and combined regorafenib treatments in preclinical models of liver and gastrointestinal cancers.Experimental & molecular medicine · 2019Review
- Acid microenvironment promotes cell survival of human bone sarcoma through the activation of cIAP proteins and NF-κB pathway.American journal of cancer research · 2019Article
- Survivin is a novel transcription regulator of KIT and is downregulated by miRNA-494 in gastrointestinal stromal tumors.International journal of cancer · 2018Article
- Recurring Amplification at 11q22.1-q22.2 Locus Plays an Important Role in Lymph Node Metastasis and Radioresistance in OSCC.Scientific reports · 2017Article
- High-Throughput Screening of Myxoid Liposarcoma Cell Lines: Survivin Is Essential for Tumor Growth.Translational oncology · 2017Article
- Current research and treatment for gastrointestinal stromal tumors.World journal of gastroenterology · 2017Review
- Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis.Autophagy · 2017Review
- Inducing death in tumor cells: roles of the inhibitor of apoptosis proteins.F1000Research · 2017Review
- Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway.Oncotarget · 2016Article
- Prognostic Significance of theCancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Gastrointestinal stromal tumors (GIST) exhibit a strong oncogenic dependency on KIT and KIT inhibitors confer long lasting disease stabilization in the majority of patients. Nonetheless, KIT inhibition alone does not cure GIST as a subset of GIST cells evade apoptosis and eventually develop resistance. Inhibitors of Apoptosis Proteins (IAPs) may confer resistance to drug-induced apoptosis. We observed that the mRNA and protein of IAPs XIAP (BIRC4) and survivin (BIRC5) were highly expressed in primary GIST tumors and cell line models. Amplification of the respective gene loci (BIRC2, BIRC3, BIRC4, BIRC5) was detected in 47% of GIST studied by SNP arrays. Whole exome analyses revealed a mutation of SMAC(DIABLO) in a heavily pretreated patient. Both, survivin (rank 62-92/11.194 tested proteins) and XIAP (rank 106-557/11.194) were found to be essential proteins for survival in a synthetic lethality screen. Expression of XIAP and survivin decreased upon KIT inhibition and may play a role in KIT-regulated pro-survival signaling. SMAC-mimetic treatment with LCL161 and TL32711 reduced cIAP1 and XIAP expression. Survivin inhibitor YM155 lead to transcriptional repression of BIRC5/survivin (YM155) and induced apoptosis. Combinational treatment with KIT inhibitors (imatinib, regorafenib) enhanced the proapoptotic effect. These findings support the combination of KIT inhibition with IAP antagonists in GIST.
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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.