ArticleAutophagy2021
The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 64 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.
A Phase I/II, Open Label Study to Assess the Efficacy and Safety of ABTL0812 in Combination With Paclitaxel and Carboplatin in Patients With Advanced Endometrial Cancer or Squamous NSCLC
A Randomized Phase I/II Open Label Study to Assess the Efficacy and Safety of ABTL0812 in Combination With Gemcitabine and Nab-paclitaxel in Patients With Advanced Metastatic Pancreatic Cancer at First Line Therapy
A Phase I Open Label Followed by a Phase II Randomized, Controlled Study to Assess the Efficacy and Safety of ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic
Who cites it
64 citing papers in PubMed, 109 citations in OpenAlex.
- Trial
- Therapeutic potential of the sphingosine kinase 2 inhibitor opaganib.Pharmaceutical science advances · 2026Review
- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Article
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Chrysosplenetin-induced TMED3 aggregation triggers unfolded protein response in pancreatic cancer.EMBO molecular medicine · 2026Article
- O-Glycosylation of E-Cadherin Induced by Endoplasmic Reticulum Stress Negatively Regulates Cell Polarity and Proliferation in Acute Kidney Injury.Journal of biochemical and molecular toxicology · 2026Article
- Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology.Journal of ovarian research · 2026Review
- HOOK2 downregulation compromises the tumorigenic and stemness properties of ovarian cancer cells by increasing endoplasmic reticulum stress.Cell death & disease · 2026Article
- Identification and validation of a sphingolipid metabolism-related prognostic signature for predicting prognosis and immune microenvironment-related characteristics in ovarian cancer.Translational cancer research · 2026Article
- MAPK ERK5 is a novel regulator of MHC-I in cancer cells.Cell communication and signaling : CCS · 2026Article
- Developing a Metabolic-Associated Prognostic Index for Risk Stratification and Therapeutic Guidance in Stage I Lung Adenocarcinoma via Multiomics Analysis.JCO precision oncology · 2026Article
- Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells.Pharmaceutical science advances · 2025Article
- TRIB3 regulates Cx43 expression in human granulosa cells via the Wnt/β-catenin signaling pathway: an in vitro study.Journal of ovarian research · 2025Article
- Autophagy in cholangiocarcinoma: a comprehensive review about roles and regulatory mechanisms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Bioactive Compounds Targeting Dihydroceramide and Their Therapeutic Potential in Cancer Treatment.Cancers · 2025Review
- Reversal of chemotherapy resistance in gastric cancer with traditional Chinese medicine as sensitizer: potential mechanism of action.Frontiers in oncology · 2025Review
- Endoplasmic reticulum stress in non-small cell lung cancer.American journal of cancer research · 2025Review
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy.Journal of experimental & clinical cancer research : CR · 2024Article
4 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
22 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma (NCT03366480). Previously, we showed that ABTL0812 induces TRIB3 pseudokinase expression, resulting in the inhibition of the AKT-MTORC1 axis and macroautophagy/autophagy-mediated cancer cell death. However, the precise molecular determinants involved in the cytotoxic autophagy caused by ABTL0812 remained unclear. Using a wide range of biochemical and lipidomic analyses, we demonstrated that ABTL0812 increases cellular long-chain dihydroceramides by impairing DEGS1 (delta 4-desaturase, sphingolipid 1) activity, which resulted in sustained ER stress and activated unfolded protein response (UPR) via ATF4-DDIT3-TRIB3 that ultimately promotes cytotoxic autophagy in cancer cells. Accordingly, pharmacological manipulation to increase cellular dihydroceramides or incubation with exogenous dihydroceramides resulted in ER stress, UPR and autophagy-mediated cancer cell death. Importantly, we have optimized a method to quantify mRNAs in blood samples from patients enrolled in the ongoing clinical trial, who showed significant increased
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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.