ArticleScience translational medicine2013
Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03034200 (Phase 2 Study of ONC201 in Neuroendocrine Tumors), which is not on this map. Cited by 224 papers, 1 of them a synthesis that pooled 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.
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.
Phase 2 Study of ONC201 in Neuroendocrine Tumors
Who cites it
224 citing papers in PubMed, 1 synthesis or guideline pooled it, 337 citations in OpenAlex.
- Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells.Neuro-oncology · 2021Pooled it
- A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.Clinical pharmacology in drug development · 2025Trial
- ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.Neuro-oncology · 2024Trial
- A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.The oncologist · 2023Trial
- Quantitation of the next-generation imipridone ONC206 in human plasma by a simple and sensitive UPLC-MS/MS assay for clinical pharmacokinetic application.Journal of pharmaceutical and biomedical analysis · 2022Trial
- Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Biological activity of weekly ONC201 in adult recurrent glioblastoma patients.Neuro-oncology · 2020Trial
- A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma.Pediatric blood & cancer · 2016Trial
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- ONC201 in combination with ATR inhibitor ceralasertib exhibits potent synergy in ovarian cancer cells.bioRxiv : the preprint server for biology · 2026Article
- ONC201 enhances the radiosensitivity of small-cell lung cancer via inhibition of the FAK signaling pathway.iScience · 2026Article
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- ONC206 demonstrates potent antitumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma.Neuro-oncology · 2026Article
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- Tumor extracellular vesicle RNA profiling predicts treatment response in pediatric diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Article
- The interplay between circadian rhythm components and apoptosis in health and disease.Human cell · 2026Review
- The role of dordaviprone in the multidisciplinary management of diffuse midline glioma.Surgical neurology international · 2026Review
164 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
13 authors at 5 institutions in 1 country.
Funding
Abstract
Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.
Indexed as
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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.