ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 100 citations in OpenAlex.
- CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses.iScience · 2025Article
- Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.International journal of molecular sciences · 2024Review
- Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.Cellular & molecular biology letters · 2024Article
- Potential New Therapies "ROS-Based" in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis.Antioxidants (Basel, Switzerland) · 2024Review
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- Emerging treatments for myelodysplastic syndromes: Biological rationales and clinical translation.Cell reports. Medicine · 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
- PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Synthesis and antitumor effects of novel benzyl naphthyl sulfoxide/sulfone derivatives derived from Rigosertib.RSC advances · 2021Article
- Therapeutic Targeting PLK1 by ON-01910.Na Is Effective in Local Treatment of Retinoblastoma.Oncology research · 2021Article
- Anti-tumor effects of rigosertib in high-risk neuroblastoma.Translational oncology · 2021Article
- Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade.Molecular cancer · 2021Article
- Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa.International journal of molecular sciences · 2021Review
- Rigosertib Induces Mitotic Arrest and Apoptosis in RAS-Mutated Rhabdomyosarcoma and Neuroblastoma.Molecular cancer therapeutics · 2021Article
- Ascorbic acid (vitamin C) synergistically enhances the therapeutic effect of targeted therapy in chronic lymphocytic leukemia.Journal of experimental & clinical cancer research : CR · 2020Article
- Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent.Molecular cell · 2020Article
- Article
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeChronic lymphocytic leukemia (CLL), a malignancy of mature B cells, is incurable with chemotherapy. Signals from the microenvironment support leukemic cell survival and proliferation and may confer chemotherapy resistance. ON 01910.Na (Rigosertib), a multikinase phosphoinositide 3-kinase (PI3K) inhibitor, is entering phase III trials for myelodysplastic syndrome. Our aim was to analyze the efficacy of ON 01910.Na against CLL cells in vitro and investigate the molecular effects of this drug on tumor biology. EXPERIMENTAL
designCytotoxicity of ON 01910.Na against CLL cells from 34 patients was determined in vitro with flow cytometry of cells stained with Annexin V and CD19. Global gene expression profiling on Affymetrix microarrays, flow cytometry, Western blotting, and cocultures with stroma cells were used to delineate ON 01910.Na mechanism of action.
resultsON 01910.Na induced apoptosis in CLL B cells without significant toxicity against T cells or normal B cells. ON 01910.Na was equally active against leukemic cells associated with a more aggressive disease course [immunoglobulin heavy-chain variable region unmutated, adverse cytogenetics] than against cells without these features. Gene expression profiling revealed two main mechanisms of action: PI3K/AKT inhibition and induction of ROS that resulted in an oxidative stress response through activating protein 1 (AP-1), c-jun-NH(2)-terminal kinase, and ATF3 culminating in the upregulation of NOXA. ROS scavengers and shRNA mediated knockdown of ATF3- and NOXA-protected cells from drug-induced apoptosis. ON 01910.Na also abrogated the prosurvival effect of follicular dendritic cells on CLL cells and reduced SDF-1-induced migration of leukemic cells.
conclusionsThese data support the clinical development of ON 01910.Na in CLL.
Indexed as
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.