Please use this identifier to cite or link to this item:
https://doi.org/10.1007/s00280-013-2132-y
DC Field | Value | |
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dc.title | Inhibiting proliferation of gefitinib-resistant, non-small cell lung cancer | |
dc.contributor.author | Sudo, M. | |
dc.contributor.author | Chin, T.M. | |
dc.contributor.author | Mori, S. | |
dc.contributor.author | Doan, N.B. | |
dc.contributor.author | Said, J.W. | |
dc.contributor.author | Akashi, M. | |
dc.contributor.author | Koeffler, H.P. | |
dc.date.accessioned | 2014-12-12T07:49:37Z | |
dc.date.available | 2014-12-12T07:49:37Z | |
dc.date.issued | 2013-05 | |
dc.identifier.citation | Sudo, M., Chin, T.M., Mori, S., Doan, N.B., Said, J.W., Akashi, M., Koeffler, H.P. (2013-05). Inhibiting proliferation of gefitinib-resistant, non-small cell lung cancer. Cancer Chemotherapy and Pharmacology 71 (5) : 1325-1334. ScholarBank@NUS Repository. https://doi.org/10.1007/s00280-013-2132-y | |
dc.identifier.issn | 03445704 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/116416 | |
dc.description.abstract | Purpose: Sensitivity to a tyrosine kinase inhibitor (TKI) is correlated with the presence of somatic mutations that affect the kinase domain of epidermal growth factor receptor (EGFR). Development of resistance to TKI is a major therapeutic problem in non-small cell lung cancer (NSCLC). Aim of this study is to identify agents that can overcome TKI resistance in NSCLC. Methods: We used a carefully selected panel of 12 NSCLC cell lines to address this clinical problem. Initially, the cell lines were treated with a variety of 10 compounds. Cellular proliferation was measured via MTT assay. We then focused on the gefitinib-resistant, EGFR mutant cell lines [H1650: exon 19 and PTEN mutations; and H1975: exons 20 (T790M) and 21 (L858R)] to identify agents that could overcome TKI resistance. Results: Both 17-DMAG (Hsp90 inhibitor) and belinostat (histone deacetylase inhibitor, HDACi) effectively decreased the growth of almost all NSCLC lines. Also, belinostat markedly decreased the expression of EGFR and phospho-Akt in the cells. Combination of 17-DMAG and belinostat synergistically inhibited in vitro proliferation of these cells. Furthermore, both agents and their combination almost completely prevented TKI-resistant tumor formation (EGFR T790M mutation) in a xenograft model. Conclusion: These results suggest that the combination of 17-DMAG and belinostat should be examined in a clinical trial for TKI-resistant NSCLC cell. © 2013 The Author(s). | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1007/s00280-013-2132-y | |
dc.source | Scopus | |
dc.subject | 17-DMAG | |
dc.subject | Belinostat | |
dc.subject | Combination chemotherapy | |
dc.subject | EGFR | |
dc.subject | Non-small cell lung cancer (NSCLC) | |
dc.subject | Tyrosine kinase inhibitor (TKI) | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.description.doi | 10.1007/s00280-013-2132-y | |
dc.description.sourcetitle | Cancer Chemotherapy and Pharmacology | |
dc.description.volume | 71 | |
dc.description.issue | 5 | |
dc.description.page | 1325-1334 | |
dc.description.coden | CCPHD | |
dc.identifier.isiut | 000318287600023 | |
Appears in Collections: | Staff Publications |
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