ArticleBritish journal of cancer2021
APR-246 induces apoptosis and enhances chemo-sensitivity via activation of ROS and TAp73-Noxa signal in oesophageal squamous cell cancer with TP53 missense mutation.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Eprenetapopt in combination with Palbociclib exerts synthetic lethality in mantle cell lymphoma.Translational oncology · 2026Article
- Fundamentals and emerging frontiers in p53-targeted drug development.Biochemistry and biophysics reports · 2026Review
- Wild-Type p53 Protein Enhances APR-246-Induced Cytotoxicity in Acute Myeloid Leukemia and Normal Hematopoietic Stem/Progenitor Cells.International journal of molecular sciences · 2026Article
- Unbiased assessment of APR-246 responsive p53 mutants in ovarian cancer.Cell death discovery · 2026Article
- Overcoming chemoresistance in esophageal cancer with synergistic strategies.Frontiers in immunology · 2026Review
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- Pharmacological Modulation of MutantBiomedicines · 2025Review
- APR-246 as a radiosensitization strategy for mutant p53 cancers treated with alpha-particles-based radiotherapy.Cell death & disease · 2024Article
- p53 biology and reactivation for improved therapy in MDS and AML.Biomarker research · 2024Review
- RYBP contributes to improved prognosis in colorectal cancer via regulation of cell cycle, apoptosis and oxaliplatin sensitivity.International journal of oncology · 2023Article
- Patient-derived tumor models: a suitable tool for preclinical studies on esophageal cancer.Cancer gene therapy · 2023Review
- PRIMA-1ACS omega · 2023Article
- The p53 reactivator PRIMA-1Investigational new drugs · 2023Article
- Simultaneous regulation of ferroptosis suppressor protein 1 and glutathione peroxidase 4 as a new therapeutic strategy of ferroptosis for esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2023Article
- Risk stratification of oesophageal squamous cell carcinoma using change in total lesion glycolysis and number of PET-positive lymph nodes.British journal of cancer · 2023Article
- The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells.Cell death and differentiation · 2023Article
- A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach.International journal of molecular sciences · 2023Review
- Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics.International journal of biological sciences · 2023Review
- Characterizing isoform switching events in esophageal adenocarcinoma.Molecular therapy. Nucleic acids · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in p53, identified in 90% of oesophageal squamous cell carcinoma (ESCC), are associated with unfavourable prognosis and chemo-resistance. APR-246 induces apoptosis by restoring transcriptional ability of mutant p53, and may be a promising therapeutic agent to overcome chemo-resistance in ESCC.
methodsIn ESCC cell lines differing in p53 status, we performed in vitro cell viability and apoptosis assays, evaluated reactive oxygen species (ROS) generation, and assessed signal changes by western blot after APR-246 administration with/without chemo-agent. Antitumour effects and signal changes were evaluated in in vivo experiments using xenograft and patient-derived xenograft (PDX) mouse models.
resultsAPR-246 administration induced significant apoptosis by upregulating p73 and Noxa via ROS induction in ESCC cell lines harbouring p53 missense mutations. Moreover, APR-246 plus chemotherapy exerted combined antitumour effects in ESCC with p53 missense mutations. This effect was also mediated through enhanced ROS activity, leading to massive apoptosis via upregulation of p73 and Noxa. These findings were confirmed by xenograft and PDX models with p53 mutant ESCC.
conclusionAPR-246 strongly induced apoptosis by inducing ROS activity and p73-Noxa signalling, specifically in ESCC with p53 missense mutation. This antitumour effect was further enhanced by combination with 5-FU, which we first confirmed in ESCC preclinical model.
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