ArticleOncotarget2017
Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses dedifferentiated papillary thyroid cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Novel antagonist APG-115 targets MDM2-p53 to induce p53-mediated apoptosis and radiosensitization in colorectal cancer.Clinical and experimental medicine · 2026Article
- DNA Damage and Repair in Thyroid Physiology and Disease.Endocrine reviews · 2026Review
- The CHK1 inhibitor Prexasertib is effective againstFrontiers in endocrinology · 2026Article
- Research Progress on Small Molecule Inhibitors of MDM2-p53 Protein-protein Interaction.Anti-cancer agents in medicinal chemistry · 2026Review
- Epigenomic Modulators and Thyroid Hormone Receptor β Agonists: A New Paradigm for Tumor Suppression in Thyroid Cancer.Endocrinology · 2025Review
- Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Parotid Metastasis in a Case of Papillary Thyroid Carcinoma: Case Report and Review of Literature.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023Article
- Review
- Enhancement of nanoparticle-mediated double suicide gene expression driven by 'E9-hTERT promoter' switch in dedifferentiated thyroid cancer cells.Bioengineered · 2021Article
- Article
- Synthesis of 1,3-diaryl-spiro[azetidine-2,3'-indoline]-2',4-dionesRSC advances · 2020Article
- GPX7 promotes the growth of human papillary thyroid carcinoma via enhancement of cell proliferation and inhibition of cell apoptosis.Translational cancer research · 2019Article
- A novel small molecule inhibitor of MDM2-p53 (APG-115) enhances radiosensitivity of gastric adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive growth, recurrence, distant metastasis, and resistance to radioactive iodine (RAI) therapy. DePTC is also accompanied by poor prognosis and high early-mortality. Nevertheless, most DePTC cells show intact p53 downstream functionality. In cells with wild-type p53, the murine double minute2 (MDM2) protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53 interaction restores p53 activity and leads to cell cycle arrest and apoptosis. Restoring p53 function by inhibiting its interaction with p53 suppressors such as MDM2 is thus a promising therapeutic strategy for the treatment of DePTC. The novel MDM2-p53 interaction antagonist APG115 is an analogue of SAR405838, and is being tested in a phase I clinical trial. In this study, we evaluated the efficacy of APG115 as a single-agent to treat DePTC. APG115 diminished the viability of p53 wild-type DePTC cells and induced cell cycle arrest and apoptosis. In a human xenograft mouse model, APG115 elicited robust tumor regression and cell apoptosis. These data demonstrate that further research is warranted to determine whether APG115 can be used to effectively treat DePTC patients.
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