ArticleOncotarget2016
ON 01910.Na (rigosertib) inhibits PI3K/Akt pathway and activates oxidative stress signals in head and neck cancer cell lines.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 47 citations in OpenAlex.
- Machine learning combined with multi-omics analysis: identifying nucleotide metabolism-associated immune genes and validating their functions in cardiomyopathy.BMC cardiovascular disorders · 2026Article
- From Carcinogenesis to Drug Resistance: The Multifaceted Role of Oxidative Stress in Head and Neck Cancer.Cancers · 2025Review
- Unlocking the therapeutic potential of rigosertib as a selective therapy for ovarian cancer.Cell reports. Medicine · 2025Article
- CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses.iScience · 2025Article
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na).Pharmaceutics · 2023Review
- Subversion of a protein-microRNA signaling pathway by hepatitis C virus.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent.International journal of molecular sciences · 2023Article
- SOD2 Enhancement by Long-Term Inhibition of the PI3K Pathway Confers Multi-Drug Resistance and Enhanced Tumor-Initiating Features in Head and Neck Cancer.International journal of molecular sciences · 2021Article
- In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells.International journal of molecular sciences · 2021Article
- Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade.Molecular cancer · 2021Article
- Mitotic Poisons in Research and Medicine.Molecules (Basel, Switzerland) · 2020Review
- Mechanism analysis of toxicity of sodium sulfite to human hepatocytes L02.Molecular and cellular biochemistry · 2020Article
- Design, Synthesis and Preliminary Biological Evaluation of Benzylsulfone Coumarin Derivatives as Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2019Article
- Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers.Lung Cancer (Auckland, N.Z.) · 2019Article
- Loss of USP28-mediated BRAF degradation drives resistance to RAF cancer therapies.The Journal of experimental medicine · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Squamous cell carcinoma of the head and neck (HNSCC) is characterized by high morbidity and mortality. Treatment failure, drug resistance and chemoradiation toxicity have necessitated the development of alternative treatment strategies. Styryl benzyl sulfones, a family of novel small molecule inhibitors, are being evaluated as anti-neoplastic agents in multiple clinical trials. The activity of these compounds has been well characterized in several preclinical tumor studies, but their activity has yet to be fully examined in HNSCC. We tested ON 01910.Na (rigosertib), a styryl benzyl sulfone in late-stage development, in HNSCC preclinical models. Rigosertib induced cytotoxicity in both HPV(+) and HPV(-) HNSCC cells in a dose-dependent manner. Characterization of the underlying molecular mechanism indicated that rigosertib induced inhibition of the PI3K/Akt/mTOR pathway, induced oxidative stress resulting in increased generation of reactive oxygen species (ROS), and activated extracellular signal-regulated kinases (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Increased phosphorylation and cytoplasmic translocation of ATF-2 were also observed following rigosertib treatment. These changes in cell signaling led us to consider combining rigosertib with HNSCC standard-of-care therapies, such as cisplatin and radiation. Our study highlights the promising preclinical activity of rigosertib in HNSCC irrespective of HPV status and provides a molecular basis for rigosertib in combination with standard of care agents for HNSCC.
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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.