Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer NSCLCReportar como inadecuado

Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer NSCLC - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 9:300

First Online: 27 August 2009Received: 23 April 2009Accepted: 27 August 2009DOI: 10.1186-1471-2407-9-300

Cite this article as: Glaysher, S., Yiannakis, D., Gabriel, F.G. et al. BMC Cancer 2009 9: 300. doi:10.1186-1471-2407-9-300


BackgroundNSCLC 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.

MethodsThe 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.

ResultsThere 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.

ConclusionGenes 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-300 contains supplementary material, which is available to authorized users.

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Autor: Sharon Glaysher - Dennis Yiannakis - Francis G Gabriel - Penny Johnson - Marta E Polak - Louise A Knight - Zoe Goldthorp


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