ArticleOncogenesis2025
ONC201 enhances the cytotoxic effect of cisplatin through ATF3/ATF4/CHOP in head and neck squamous cell carcinoma cells.
Article in Oncogenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- Heteronemin suppresses chemoresistant oral squamous cell carcinoma cells through ROS-mediated apoptosis and cuproptosis-associated mitochondrial stress.Apoptosis : an international journal on programmed cell death · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) remains a prevalent and challenging cancer to treat due to its genetic heterogeneity. Cisplatin resistance is one of important causes in treatment failure of locally advanced HNSCC. ONC201, a selective dopamine receptor D2 antagonist and mitochondrial ClpP agonist, has emerged as a potential antitumor agent in various malignancies. This study explores the therapeutic potential of ONC201, alone and in combination with cisplatin, in both cisplatin-sensitive and -resistant HNSCC cells, with an emphasis on endoplasmic reticulum (ER) stress-mediated apoptosis. A cisplatin-resistant HNSCC subline (OC2-CR1) was developed via long-term drug exposure. The treatment effectiveness of ONC201 alone and cisplatin in combination on cell viability, DNA damage, reactive oxygen species (ROS) production, and stress response markers were evaluated. ONC201 exhibited potent cytotoxicity in both cisplatin-sensitive and -resistant HNSCC cells, retaining efficacy in OC2-CR1 cells. Combined treatment with ONC201 and cisplatin demonstrated synergistic inhibition of proliferation and migration, with enhanced induction of apoptosis. Mechanistically, ONC201 induced ER stress-mediated cell death via ATF4/CHOP signaling in cisplatin-sensitive cells, while ATF3/CHOP predominated in resistant cells. In vivo, combination therapy significantly suppressed tumor growth in xenograft models, including cisplatin-resistant tumors, without inducing toxicity. Immunohistochemical analysis confirmed activation of CHOP in tumor tissues. Furthermore, clinical correlation revealed that low CHOP expression in OSCC patients was associated with increased recurrence risk and inferior recurrence-free survival significantly. This study provides compelling evidence that ONC201 enhances cisplatin efficacy through distinct, stress-mediated apoptotic pathways in HNSCC. The ability of ONC201 to overcome cisplatin resistance and its synergistic antitumor effects highlight its promise as a candidate for combination therapy. These findings support the translational potential of targeting the ATF3/ATF4/CHOP axis to improve outcomes in patients with cisplatin resistant HNSCC.
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.