Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC)

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aut.relation.startpage300
aut.relation.volume9
dc.contributor.authorGlaysher, S
dc.contributor.authorYiannakis, D
dc.contributor.authorGabriel, FG
dc.contributor.authorJohnson, P
dc.contributor.authorPolak, ME
dc.contributor.authorKnight, LA
dc.contributor.authorGoldthorpe, Z
dc.contributor.authorPeregrin, K
dc.contributor.authorGyi, M
dc.contributor.authorModi, P
dc.contributor.authorRahamim, J
dc.contributor.authorSmith, ME
dc.contributor.authorAmer, K
dc.contributor.authorAddis, B
dc.contributor.authorPoole, M
dc.contributor.authorNarayanan, A
dc.contributor.authorGulliford, TJ
dc.contributor.authorAndreotti, PE
dc.contributor.authorCree, IA
dc.date.accessioned2014-12-04T23:59:33Z
dc.date.available2014-12-04T23:59:33Z
dc.date.copyright2009
dc.date.issued2009
dc.description.abstractBackground NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.
dc.identifier.citationBMC Cancer 2009, 9:300. DOI:10.1186/1471-2407-9-300
dc.identifier.doi10.1186/1471-2407-9-300
dc.identifier.issn1471-2407
dc.identifier.roid13574en_NZ
dc.identifier.urihttps://hdl.handle.net/10292/8195
dc.languageeng
dc.publisherBioMed Central
dc.relation.urihttp://dx.doi.org/10.1186/1471-2407-9-300
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.accessrightsOpenAccess
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAntineoplastic agents
dc.subjectCarcinoma
dc.subjectNon-small-cell lung
dc.subjectDrug resistance
dc.subjectNeoplasm
dc.subjectDrug screening assays
dc.subjectAntitumor
dc.subjectFemale
dc.subjectGene expression regulation
dc.subjectNeoplastic
dc.subjectHumans
dc.subjectLung neoplasms
dc.subjectMale
dc.subjectMiddle aged
dc.titleResistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC)
dc.typeJournal Article
pubs.elements-id13037
pubs.organisational-data/AUT
pubs.organisational-data/AUT/Design & Creative Technologies
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