Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.canlet.2017.12.030
Title: Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling
Authors: Wang, 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 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Panobinostat
Histone deacetylase inhibitors
LBH589
Non-small cell lung cancer
Epigenetic therapy
HISTONE DEACETYLASE INHIBITORS
DNA-DAMAGE
1ST-LINE TREATMENT
OPEN-LABEL
PHASE-I
CHEMOTHERAPY
MULTICENTER
ERLOTINIB
METAANALYSIS
Issue Date: 28-Mar-2018
Publisher: ELSEVIER IRELAND LTD
Citation: Wang, 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
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.
Source Title: CANCER LETTERS
URI: https://scholarbank.nus.edu.sg/handle/10635/175506
ISSN: 03043835
18727980
DOI: 10.1016/j.canlet.2017.12.030
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