Please use this identifier to cite or link to this item:
|Title:||Inhibiting proliferation of gefitinib-resistant, non-small cell lung cancer|
Non-small cell lung cancer (NSCLC)
Tyrosine kinase inhibitor (TKI)
|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|
|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).|
|Source Title:||Cancer Chemotherapy and Pharmacology|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 19, 2019
WEB OF SCIENCETM
checked on Feb 11, 2019
checked on Jan 11, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.