Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.canlet.2017.12.030
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dc.titlePan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling
dc.contributor.authorWang, Lingzhi
dc.contributor.authorSyn, Nicholas Li-Xun
dc.contributor.authorSubhash, Vinod Vijay
dc.contributor.authorAny, Yijia
dc.contributor.authorThuya, Win Lwin
dc.contributor.authorCheow, Esther Sok Hwee
dc.contributor.authorKong, Li Ren
dc.contributor.authorYu, Fenggang
dc.contributor.authorPeethala, Praveen C.
dc.contributor.authorWong, Andrea Li-Ann
dc.contributor.authorLaljibhai, Hirpara J.
dc.contributor.authorChinnathambi, Arunachalam
dc.contributor.authorOng, Pei Shi
dc.contributor.authorHo, Paul Chi-Lui
dc.contributor.authorSethi, Gautam
dc.contributor.authorYong, Wei Peng
dc.contributor.authorGoh, Boon Cher
dc.date.accessioned2020-09-10T01:55:38Z
dc.date.available2020-09-10T01:55:38Z
dc.date.issued2018-03-28
dc.identifier.citationWang, Lingzhi, Syn, Nicholas Li-Xun, Subhash, Vinod Vijay, Any, Yijia, Thuya, Win Lwin, Cheow, Esther Sok Hwee, Kong, Li Ren, Yu, Fenggang, Peethala, Praveen C., Wong, Andrea Li-Ann, Laljibhai, Hirpara J., Chinnathambi, Arunachalam, Ong, Pei Shi, Ho, Paul Chi-Lui, Sethi, Gautam, Yong, Wei Peng, Goh, Boon Cher (2018-03-28). Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling. CANCER LETTERS 417 : 152-160. ScholarBank@NUS Repository. https://doi.org/10.1016/j.canlet.2017.12.030
dc.identifier.issn03043835
dc.identifier.issn18727980
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175506
dc.description.abstract© 2018 Elsevier B.V. Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chemotherapy, suggesting a rational pairing of HDAC inhibitors with DNA damaging chemotherapeutic agents in the treatment of human malignancies. Here we report that panobinostat (LBH589), a potent pan-HDAC inhibitor, effectively curbed the proliferation of non-small cell lung cancer (NSCLC) cell lines A549, Calu-1, H226, H460, H838 and SKMES-1 at IC50 concentrations between 4 and 31 nmol/L via pleiotropic mechanisms, including crosstalk with EGFR signal transduction cascades. Combination therapy with carboplatin elicited rapid tumor cell kill and effectively restrained anchorage-independent clonogenic survival to a considerably greater extent over either monotherapy. The administration of carboplatin and panobinostat at clinically relevant doses to NOD-SCID xenograft mice drastically stalled disease progression by 92% as compared with negative control (P =.0026), which was greater than the 28% and 54% achieved with either carboplatin (P =.220) or panobinostat (P =.017) alone. These data demonstrate that panobinostat has strong anti-NSCLC activity and chemosensitizes tumors to carboplatin, thus justifying further evaluation of this combination approach in clinical trials.
dc.language.isoen
dc.publisherELSEVIER IRELAND LTD
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectPanobinostat
dc.subjectHistone deacetylase inhibitors
dc.subjectLBH589
dc.subjectNon-small cell lung cancer
dc.subjectEpigenetic therapy
dc.subjectHISTONE DEACETYLASE INHIBITORS
dc.subjectDNA-DAMAGE
dc.subject1ST-LINE TREATMENT
dc.subjectOPEN-LABEL
dc.subjectPHASE-I
dc.subjectCHEMOTHERAPY
dc.subjectMULTICENTER
dc.subjectERLOTINIB
dc.subjectMETAANALYSIS
dc.typeArticle
dc.date.updated2020-09-09T22:28:53Z
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentDEPT OF PHARMACY
dc.description.doi10.1016/j.canlet.2017.12.030
dc.description.sourcetitleCANCER LETTERS
dc.description.volume417
dc.description.page152-160
dc.published.statePublished
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