Please use this identifier to cite or link to this item:
https://doi.org/10.1186/s13045-017-0540-x
DC Field | Value | |
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dc.title | Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets | |
dc.contributor.author | Kanojia, D | |
dc.contributor.author | Garg, M | |
dc.contributor.author | Martinez, J | |
dc.contributor.author | Anand, M.T | |
dc.contributor.author | Luty, S.B | |
dc.contributor.author | Doan, N.B | |
dc.contributor.author | Said, J.W | |
dc.contributor.author | Forscher, C | |
dc.contributor.author | Tyner, J.W | |
dc.contributor.author | Koeffler, H.P | |
dc.date.accessioned | 2020-09-01T00:48:46Z | |
dc.date.available | 2020-09-01T00:48:46Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Kanojia, 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.issn | 17568722 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/173760 | |
dc.description.abstract | Background: 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.source | Unpaywall 20200831 | |
dc.subject | 4 amino 5 (3 benzyloxyphenyl) 7 [3 (1 pyrrolidinylmethyl)cyclobutyl] 7h pyrrolo[2,3 d]pyrimidine | |
dc.subject | bortezomib | |
dc.subject | CD135 antigen | |
dc.subject | dasatinib | |
dc.subject | elesclomol | |
dc.subject | ephrin receptor A6 | |
dc.subject | epidermal growth factor receptor | |
dc.subject | focal adhesion kinase 1 | |
dc.subject | Janus kinase 1 | |
dc.subject | Janus kinase 2 | |
dc.subject | macrophage stimulating 1 receptor | |
dc.subject | megakaryocyte associated tyrosine kinase | |
dc.subject | phosphotransferase | |
dc.subject | platelet derived growth factor alpha receptor | |
dc.subject | ponatinib | |
dc.subject | protein kinase Fer | |
dc.subject | protein kinase Syk | |
dc.subject | protein tyrosine kinase | |
dc.subject | protein tyrosine kinase inhibitor | |
dc.subject | receptor tyrosine kinase like orphan receptor 1 | |
dc.subject | RNA | |
dc.subject | ROS protooncogene 1 receptor tyrosine kinase | |
dc.subject | serine threonine tyrosine kinase 1 | |
dc.subject | staurosporine | |
dc.subject | tanespimycin | |
dc.subject | tumor protein | |
dc.subject | unclassified drug | |
dc.subject | v kit Hardy Zuckerman 4 feline sarcoma viral oncogene homolog protein | |
dc.subject | vasculotropin receptor 2 | |
dc.subject | imidazole derivative | |
dc.subject | ponatinib | |
dc.subject | protein kinase inhibitor | |
dc.subject | pyridazine derivative | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | antineoplastic activity | |
dc.subject | apoptosis | |
dc.subject | Article | |
dc.subject | cancer growth | |
dc.subject | cell cycle arrest | |
dc.subject | cell cycle G0 phase | |
dc.subject | cell cycle G1 phase | |
dc.subject | cell cycle S phase | |
dc.subject | clonogenesis | |
dc.subject | concentration response | |
dc.subject | controlled study | |
dc.subject | drug potency | |
dc.subject | drug screening | |
dc.subject | enzyme analysis | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | IC50 | |
dc.subject | in vitro study | |
dc.subject | in vivo study | |
dc.subject | liposarcoma | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | protein targeting | |
dc.subject | RNA interference | |
dc.subject | signal transduction | |
dc.subject | animal | |
dc.subject | cell proliferation | |
dc.subject | liposarcoma | |
dc.subject | nonobese diabetic mouse | |
dc.subject | preclinical study | |
dc.subject | RNA interference | |
dc.subject | SCID mouse | |
dc.subject | Animals | |
dc.subject | Cell Proliferation | |
dc.subject | Drug Evaluation, Preclinical | |
dc.subject | Humans | |
dc.subject | Imidazoles | |
dc.subject | Liposarcoma | |
dc.subject | Mice | |
dc.subject | Mice, Inbred NOD | |
dc.subject | Mice, SCID | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Pyridazines | |
dc.subject | RNA Interference | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.1186/s13045-017-0540-x | |
dc.description.sourcetitle | Journal of Hematology and Oncology | |
dc.description.volume | 10 | |
dc.description.issue | 1 | |
dc.description.page | 173 | |
Appears in Collections: | Staff Publications Elements |
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