A gene expression profile indicative of early stage HER2 targeted therapy response

Hdl Handle:
http://hdl.handle.net/10147/298261
Title:
A gene expression profile indicative of early stage HER2 targeted therapy response
Authors:
O’Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O’Connor, Robert
Citation:
Molecular Cancer. 2013 Jul 01;12(1):69
Issue Date:
1-Jul-2013
URI:
http://dx.doi.org/10.1186/1476-4598-12-69; http://hdl.handle.net/10147/298261
Abstract:
Abstract Background Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Results Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. Conclusions In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorO’Neill, Fiona-
dc.contributor.authorMadden, Stephen F-
dc.contributor.authorClynes, Martin-
dc.contributor.authorCrown, John-
dc.contributor.authorDoolan, Padraig-
dc.contributor.authorAherne, Sinéad T-
dc.contributor.authorO’Connor, Robert-
dc.date.accessioned2013-08-14T15:59:55Z-
dc.date.available2013-08-14T15:59:55Z-
dc.date.issued2013-07-01-
dc.identifier.citationMolecular Cancer. 2013 Jul 01;12(1):69-
dc.identifier.urihttp://dx.doi.org/10.1186/1476-4598-12-69-
dc.identifier.urihttp://hdl.handle.net/10147/298261-
dc.description.abstractAbstract Background Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Results Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. Conclusions In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.-
dc.titleA gene expression profile indicative of early stage HER2 targeted therapy response-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderFiona O’Neill et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2013-07-27T03:08:30Z-
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