ArticleLeukemia2014
Inhibitor of apoptosis proteins as therapeutic targets in multiple myeloma.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 54 citations in OpenAlex.
- Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis.Blood advances · 2021Trial
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- Targeting the Ubiquitin-Proteasome System for Cancer.MedComm · 2025Review
- The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development.Apoptosis : an international journal on programmed cell death · 2025Review
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Regulatory role of E3 ubiquitin ligases in multiple myeloma: from molecular mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- SMAC mimetics induce human macrophages to phagocytose live cancer cells.Immunotherapy advances · 2025Article
- The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.Scientific reports · 2024Article
- Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis.International journal of molecular sciences · 2023Article
- LCL161 enhances expansion and survival of engineered anti-tumor T cells but is restricted by death signaling.Frontiers in immunology · 2023Article
- BRCA mutations lead to XIAP overexpression and sensitise ovarian cancer to inhibitor of apoptosis (IAP) family inhibitors.British journal of cancer · 2022Article
- IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-κB- and caspase-8-dependent mechanisms.Blood advances · 2021Article
- Review
- Future Therapeutic Directions for Smac-Mimetics.Cells · 2020Review
- The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy.Cells · 2020Review
- Proteomic Level Changes on Treatment in MCF-7/DDP Breast Cancer Drug- Resistant Cells.Anti-cancer agents in medicinal chemistry · 2020Article
- SM‑164 enhances the antitumor activity of adriamycin in human U2‑OS cells via downregulation of X‑linked inhibitor of apoptosis protein.Molecular medicine reports · 2019Article
- Review
- Modulation of Respiration and Mitochondrial Dynamics by SMAC-Mimetics for Combination Therapy in Chemoresistant Cancer.Theranostics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The inhibitor of apoptosis (IAP) proteins have a critical role in the control of apoptotic machinery, and has been explored as a therapeutic target. Here, we have examined the functional importance of IAPs in multiple myeloma (MM) by using a Smac (second mitochondria-derived activator of caspases)-mimetic LCL161. We observed that LCL161 was able to potently induce apoptosis in some MM cell lines but not in others. Examining the levels of X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein 2 (cIAP2) post LCL161 treatment indicated clear downregulation of both XIAP activity and cIAP1 levels in both the sensitive and less sensitive (resistant) cell lines. cIAP2, however, was not downregulated in the cell line resistant to the drug. Small interfering RNA-mediated silencing of cIAP2 significantly enhanced the effect of LCL161, indicating the importance of downregulation of all IAPs simultaneously for induction of apoptosis in MM cells. LCL161 induced marked up regulation of the Jak2/Stat3 pathway in the resistant MM cell lines. Combining LCL161 with a Jak2-specific inhibitor resulted in synergistic cell death in MM cell lines and patient cells. In addition, combining LCL161 with death-inducing ligands clearly showed that LCL161 sensitized MM cells to both Fas-ligand and TRAIL.
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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.