Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13045-017-0540-x
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dc.titleKinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets
dc.contributor.authorKanojia, D
dc.contributor.authorGarg, M
dc.contributor.authorMartinez, J
dc.contributor.authorAnand, M.T
dc.contributor.authorLuty, S.B
dc.contributor.authorDoan, N.B
dc.contributor.authorSaid, J.W
dc.contributor.authorForscher, C
dc.contributor.authorTyner, J.W
dc.contributor.authorKoeffler, H.P
dc.date.accessioned2020-09-01T00:48:46Z
dc.date.available2020-09-01T00:48:46Z
dc.date.issued2017
dc.identifier.citationKanojia, D, Garg, M, Martinez, J, Anand, M.T, Luty, S.B, Doan, N.B, Said, J.W, Forscher, C, Tyner, J.W, Koeffler, H.P (2017). Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets. Journal of Hematology and Oncology 10 (1) : 173. ScholarBank@NUS Repository. https://doi.org/10.1186/s13045-017-0540-x
dc.identifier.issn17568722
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173760
dc.description.abstractBackground: Liposarcoma, the most common soft tissue tumor, is understudied cancer, and limited progress has been made in the treatment of metastatic disease. The Achilles heel of cancer often is their kinases that are excellent therapeutic targets. However, very limited knowledge exists of therapeutic critical kinase targets in liposarcoma that could be potentially used in disease management. Methods: Large RNAi and small-molecule tyrosine kinase inhibitor screens were performed against the proliferative capacity of liposarcoma cell lines of different subtypes. Each small molecule inhibitor was either FDA approved or in a clinical trial. Results: Screening assays identified several previously unrecognized targets including PTK2 and KIT in liposarcoma. We also observed that ponatinib, multi-targeted tyrosine kinase inhibitor, was the most effective drug with anti-growth effects against all cell lines. In vitro assays showed that ponatinib inhibited the clonogenic proliferation of liposarcoma, and this anti-growth effect was associated with apoptosis and cell cycle arrest at the G0/G1 phase as well as a decrease in the KIT signaling pathway. In addition, ponatinib inhibited in vivo growth of liposarcoma in a xenograft model. Conclusions: Two large-scale kinase screenings identified novel liposarcoma targets and a FDA-approved inhibitor, ponatinib with clear anti-liposarcoma activity highlighting its potential therapy for treatment of this deadly tumor. © 2017 The Author(s).
dc.sourceUnpaywall 20200831
dc.subject4 amino 5 (3 benzyloxyphenyl) 7 [3 (1 pyrrolidinylmethyl)cyclobutyl] 7h pyrrolo[2,3 d]pyrimidine
dc.subjectbortezomib
dc.subjectCD135 antigen
dc.subjectdasatinib
dc.subjectelesclomol
dc.subjectephrin receptor A6
dc.subjectepidermal growth factor receptor
dc.subjectfocal adhesion kinase 1
dc.subjectJanus kinase 1
dc.subjectJanus kinase 2
dc.subjectmacrophage stimulating 1 receptor
dc.subjectmegakaryocyte associated tyrosine kinase
dc.subjectphosphotransferase
dc.subjectplatelet derived growth factor alpha receptor
dc.subjectponatinib
dc.subjectprotein kinase Fer
dc.subjectprotein kinase Syk
dc.subjectprotein tyrosine kinase
dc.subjectprotein tyrosine kinase inhibitor
dc.subjectreceptor tyrosine kinase like orphan receptor 1
dc.subjectRNA
dc.subjectROS protooncogene 1 receptor tyrosine kinase
dc.subjectserine threonine tyrosine kinase 1
dc.subjectstaurosporine
dc.subjecttanespimycin
dc.subjecttumor protein
dc.subjectunclassified drug
dc.subjectv kit Hardy Zuckerman 4 feline sarcoma viral oncogene homolog protein
dc.subjectvasculotropin receptor 2
dc.subjectimidazole derivative
dc.subjectponatinib
dc.subjectprotein kinase inhibitor
dc.subjectpyridazine derivative
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcancer growth
dc.subjectcell cycle arrest
dc.subjectcell cycle G0 phase
dc.subjectcell cycle G1 phase
dc.subjectcell cycle S phase
dc.subjectclonogenesis
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectdrug potency
dc.subjectdrug screening
dc.subjectenzyme analysis
dc.subjecthuman
dc.subjecthuman cell
dc.subjectIC50
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectliposarcoma
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein targeting
dc.subjectRNA interference
dc.subjectsignal transduction
dc.subjectanimal
dc.subjectcell proliferation
dc.subjectliposarcoma
dc.subjectnonobese diabetic mouse
dc.subjectpreclinical study
dc.subjectRNA interference
dc.subjectSCID mouse
dc.subjectAnimals
dc.subjectCell Proliferation
dc.subjectDrug Evaluation, Preclinical
dc.subjectHumans
dc.subjectImidazoles
dc.subjectLiposarcoma
dc.subjectMice
dc.subjectMice, Inbred NOD
dc.subjectMice, SCID
dc.subjectProtein Kinase Inhibitors
dc.subjectPyridazines
dc.subjectRNA Interference
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentMEDICINE
dc.description.doi10.1186/s13045-017-0540-x
dc.description.sourcetitleJournal of Hematology and Oncology
dc.description.volume10
dc.description.issue1
dc.description.page173
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