ArticleNature cancer2022
cFLIP suppression and DR5 activation sensitize senescent cancer cells to senolysis.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 55 citations in OpenAlex.
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Epithelial cancer cells co-opt the death ligand TRAIL to avert extrinsic apoptosis while acquiring killing capacity.Cell death and differentiation · 2026Article
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- Article
- Inducible CRISPR-Cas9 screening platform to interrogate non-proliferative cellular states.Nature protocols · 2026Review
- Investigating non-proliferative cell states with inducible CRISPR screens.Nature protocols · 2026Article
- Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability.Nature cell biology · 2026Article
- Multi-Omics and Machine Learning-Uncovered FLT1-Mediated Epithelial-Endothelial Crosstalk in Cellular Senescence Driving Clear Cell Renal Cell Carcinoma Malignancy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- IAP Antagonists Selectively Eliminate Therapy-Induced Senescent Cancer Cells via TNFα-Independent Apoptosis.Cancer science · 2026Article
- DR5/WDR12 balances p65 stability promoting sunitinib resistance in renal cell carcinoma.Cell death and differentiation · 2026Article
- EIF1AX Nucleolar Condensates Enhance Susceptibilities for the Management of Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Temozolomide-induced senescent glioblastoma cells acquire sensitivity to TRAIL death receptor 5-mediated apoptosis.Medical oncology (Northwood, London, England) · 2025Article
- SIRT5-mediated desuccinylation of MTHFD2 enhances chemoresistance in breast cancer cells by reducing therapy-induced senescence.Communications biology · 2025Article
- CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in Lung Cancer Treatment: Integrating Immunotherapy and Chinese Herbal Medicines to Enhance Immune Response.Chinese journal of integrative medicine · 2025Review
- Osalmid sensitizes clear cell renal cell carcinoma to navitoclax through a STAT3/BCL-XL pathway.Cancer letters · 2025Article
- Senescence-associated lineage-aberrant plasticity evokes T-cell-mediated tumor control.Nature communications · 2025Article
- Immune therapeutic strategies for the senescent tumor microenvironment.British journal of cancer · 2025Review
Corrections and comments
- Commented on by
Authors and funding
26 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senolytics, drugs that kill senescent cells, have been proposed to improve the response to pro-senescence cancer therapies; however, this remains challenging due to a lack of broadly acting senolytic drugs. Using CRISPR/Cas9-based genetic screens in different senescent cancer cell models, we identify loss of the death receptor inhibitor cFLIP as a common vulnerability of senescent cancer cells. Senescent cells are primed for apoptotic death by NF-κB-mediated upregulation of death receptor 5 (DR5) and its ligand TRAIL, but are protected from death by increased cFLIP expression. Activation of DR5 signaling by agonistic antibody, which can be enhanced further by suppression of cFLIP by BRD2 inhibition, leads to efficient killing of a variety of senescent cancer cells. Moreover, senescent cells sensitize adjacent non-senescent cells to killing by DR5 agonist through a bystander effect mediated by secretion of cytokines. We validate this 'one-two punch' cancer therapy by combining pro-senescence therapy with DR5 activation in different animal models.
Indexed as
Identifiers
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.