Trial reportNature medicine2016
IAP antagonists induce anti-tumor immunity in multiple myeloma.
Trial report in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
119 citing papers in PubMed, 171 citations in OpenAlex.
- Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis.Blood advances · 2021Trial
- Uncoupled bone remodeling drives myeloma bone disease in Vk*MYC mouse model of multiple myeloma.Bone reports · 2026Article
- Hematopoietic expression of cIAP2 drives inflammation and heart failure after myocardial infarction.Nature cardiovascular research · 2026Article
- A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- 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
- Preclinical and first-in-human of purinostat mesylate, a novel selective HDAC I/IIb inhibitor, in relapsed/refractory multiple myeloma and lymphoma.Signal transduction and targeted therapy · 2025Article
- BIRC2 blockade facilitates immunotherapy of hepatocellular carcinoma.Molecular cancer · 2025Article
- Article
- Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer.Nature communications · 2025Article
- Immunocompetent mouse models of multiple myeloma.Seminars in hematology · 2025Review
- Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity.Journal of translational internal medicine · 2025Article
- SMAC mimetics induce human macrophages to phagocytose live cancer cells.Immunotherapy advances · 2025Article
- 3D Tumor Model to Study Immune Cell Infiltration.Methods in molecular biology (Clifton, N.J.) · 2025Article
- 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
- Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.Genes & diseases · 2024Review
- Multifaceted Evaluation of Inhibitors of Anti-Apoptotic Proteins in Head and Neck Cancer: Insights from In Vitro, In Vivo, and Clinical Studies (Review).Pharmaceuticals (Basel, Switzerland) · 2024Review
- SMAC mimetic drives microglia phenotype and glioblastoma immune microenvironment.Cell death & disease · 2024Article
- Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds.Cell death & disease · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
59 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
27 authors at 4 institutions in 1 country.
Funding
Abstract
The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.
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What OpenQuestion holds
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.