ArticleLeukemia research2012
Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na.
Article in Leukemia research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 20 papers.
What it found
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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.
A Pilot Study of the Safety and Activity of Escalating Doses of ON 01910.Na in Patients With RAEB-1 AND RAEB-2 Myelodysplastic Syndrome (MDS) and AML With Trisomy 8
Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients With Myelodysplastic Syndrome With Excess Blasts Progressing On or After Azacitidine or Decitabine
Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na).Pharmaceutics · 2023Review
- Synthesis and antitumor effects of novel benzyl naphthyl sulfoxide/sulfone derivatives derived from Rigosertib.RSC advances · 2021Article
- Targeting the Microenvironment in MDS: The Final Frontier.Frontiers in pharmacology · 2020Review
- Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers.Lung Cancer (Auckland, N.Z.) · 2019Article
- Molecular pathophysiology of the myelodysplastic syndromes: insights for targeted therapy.Blood advances · 2018Review
- Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents.Hematology. American Society of Hematology. Education Program · 2017Review
- Novel Therapies for Acute Myeloid Leukemia: Are We Finally Breaking the Deadlock?Targeted oncology · 2017Review
- ON 01910.Na (rigosertib) inhibits PI3K/Akt pathway and activates oxidative stress signals in head and neck cancer cell lines.Oncotarget · 2016Article
- Clinical Prognostic Factors in 86 Chinese Patients with Primary Myelodysplastic Syndromes and Trisomy 8: A Single Institution Experience.Yonsei medical journal · 2016Article
- -7/7q- syndrome in myeloid-lineage hematopoietic malignancies: attempts to understand this complex disease entity.Oncogene · 2015Review
- Novel drugs for older patients with acute myeloid leukemia.Leukemia · 2015Review
- Rigosertib induces cell death of a myelodysplastic syndrome-derived cell line by DNA damage-induced G2/M arrest.Cancer science · 2015Article
- BIIB021, an Hsp90 inhibitor, effectively kills a myelodysplastic syndrome cell line via the activation of caspases and inhibition of PI3K/Akt and NF-κB pathway proteins.Experimental and therapeutic medicine · 2014Article
- Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models.Molecular cancer therapeutics · 2014Article
- Real-time nanoscale proteomic analysis of the novel multi-kinase pathway inhibitor rigosertib to measure the response to treatment of cancer.Expert opinion on investigational drugs · 2013Review
- Phase I study of ON 01910.Na (Rigosertib), a multikinase PI3K inhibitor in relapsed/refractory B-cell malignancies.Leukemia · 2013Article
- Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes.British journal of haematology · 2013Article
- Signal transduction inhibitors in treatment of myelodysplastic syndromes.Journal of hematology & oncology · 2013Review
- Hydrothiolation of benzyl mercaptan to arylacetylene: application to the synthesis of (E) and (Z)-isomers of ON 01910·Na (Rigosertib®), a phase III clinical stage anti-cancer agent.Organic & biomolecular chemistry · 2013Article
- Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.American journal of cancer research · 2013Article
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundWe previously demonstrated upregulation of c-myc, survivin, and cyclin D1 in CD34+ bone marrow mononuclear cells (BMMNCs) of patients with trisomy 8 and monosomy 7 myelodysplastic syndromes (MDS). "Knockdown" of cyclin D1 by RNA interference decreased trisomy 8 cell growth, suggesting that this might be a therapeutic target in MDS. EXPERIMENTAL
designWe performed preclinical studies using BMMNCs from patients with MDS and AML to examine the effects of the styryl sulfone ON 01910.Na on cyclin D1 accumulation, aneuploidy, and CD34+ blast percentage. We next treated twelve patients with higher risk MDS and two trisomy 8 AML patients with ON 01910.Na on a phase I clinical protocol (NCT00533416).
resultsON 01910.Na inhibited cyclin D1 expression, and was selectively toxic to trisomy 8 cells in vitro. Flow cytometry studies demonstrated increased mature CD15+ myeloid cells and decreased CD34+ blasts. Three patients treated with ON 01910.Na on a clinical had decreased bone marrow blasts by ≥ 50%, and three patients had hematologic improvements, one of which was sustained for 33 months. Patients with hematologic responses to ON 01910.Na had decreased cyclin D1 expression in their CD34+ cells.
conclusionsThe preclinical results and responses of patients on a clinical trial warrant further investigation of ON 01910.Na as a potential novel targeted therapy for higher risk MDS patients.
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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.