Evidence map›Paper›PMID 40419770›Full record

ArticleNature chemical biology2025

Tegavivint triggers TECR-dependent nonapoptotic cancer cell death.

Logan Leak, Ziwei Wang, Alby J Joseph, Brianna Johnson, Alyssa A Chan, Cassandra M Decosto, Leslie Magtanong, Pin-Joe Ko, Weaverly Colleen Lee, Joan Ritho and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
  4. A fat-fueled fatality.Nature chemical biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Logan LeakDepartment of Biology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7000-9612
Ziwei WangDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9994-1331
Alby J JosephDepartment of Biology, Stanford University, Stanford, CA, USA.
Brianna JohnsonDepartment of Biology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3214-284X
Alyssa A ChanDepartment of Biology, Stanford University, Stanford, CA, USA.
Cassandra M DecostoDepartment of Biology, Stanford University, Stanford, CA, USA.
Leslie MagtanongDepartment of Biology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-0894-3156
Pin-Joe KoDepartment of Biology, Stanford University, Stanford, CA, USA.
Weaverly Colleen LeeDepartment of Biology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9447-1174
Joan RithoDepartment of Biology, Stanford University, Stanford, CA, USA.
Sophia ManukianDepartment of Biology, Stanford University, Stanford, CA, USA.
Alec MillnerDepartment of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Shweta ChitkaraDepartment of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Jennifer J SalinasDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Rachid SkoutaDepartment of Chemistry, University of Massachusetts, Amherst, Amherst, MA, USA.
Matthew G ReesBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Melissa M RonanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jennifer A RothBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Chad L MyersDepartment of Computer Science and Engineering, Bioinformatics and Computational Biology Graduate Program, University of Minnesota-Twin Cities, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-1026-5972
Jason MoffatProgram in Genetics & Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-5663-8586
Charles BooneDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-3542-6760
Steven J BensingerDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-9657-4206
David A NathansonDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
G Ekin Atilla-GokcumenDepartment of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Everett J ModingDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7913-5351
Scott J DixonDepartment of Biology, Stanford University, Stanford, CA, USA. sjdixon@stanford.edu.ORCID http://orcid.org/0000-0001-6230-8199

Funding

UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5M
Mapping the reference genetic network of a eukaryotic cellR01HG005853 · NHGRI · UNIVERSITY OF TORONTO · PI ANDREWS, BRENDA JEAN, BOONE, CHARLES · 2010 to 2025
$7.6M
CDKN2A couples lipid metabolism to ferroptosis in glioblastomaR01NS121319 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENSINGER, STEVEN J, DIXON, SCOTT · 2021 to 2025
$2.5M
Triggering a New Cancer Cell Death Mechanism in SarcomaR01CA272485 · NCI · STANFORD UNIVERSITY · PI Scott Dixon · 2023 to 2026
$1.8M
Investigating non-apoptotic cell death in glioblastomaR01NS143119 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Scott Dixon, David A. Nathanson · 2025 to 2026
$1.2M
Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT-GMX463531National Science Foundation (NSF) MCB 2314338NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA272485NCI NIH HHS T32 CA009056NINDS NIH HHS R01 NS121319NINDS NIH HHS R01 NS143119U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA272485U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HG005853U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01NS121319
6 · The paper itself

Abstract

Small molecules that induce nonapoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here we report that tegavivint, a drug candidate undergoing human clinical trials, can activate a unique mechanism of nonapoptotic cell death in sarcomas and other cancer cells. This lethal mechanism is distinct from ferroptosis, necroptosis and pyroptosis and requires the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase (TECR). TECR is canonically involved in the synthesis of very-long-chain fatty acids but appears to promote nonapoptotic cell death in response to CIL56 and tegavivint via the synthesis of the saturated long-chain fatty acid palmitate. These findings outline a lipid-dependent nonapoptotic cell death mechanism that can be induced by a drug candidate currently being tested in humans.

Indexed as

Antineoplastic AgentsCell DeathNeoplasmsCell Line, TumorHumansAntineoplastic Agents

Identifiers

PMID40419770
PMCPMC13119621

What Socratic holds

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Read underepoch 390

Registered trials

None linked

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 Socratic graph.