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BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

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

Authors: Sharon Glaysher, Dennis Yiannakis, Francis G Gabriel, Penny Johnson, Marta E Polak, Louise A Knight, Zoe Goldthorpe, Katharine Peregrin, Mya Gyi, Paul Modi, Joe Rahamim, Mark E Smith, Khalid Amer, Bruce Addis, Matthew Poole, Ajit Narayanan, Tim J Gulliford, Peter E Andreotti, Ian A Cree

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

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.
Appendix
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Metadata
Title
Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC)
Authors
Sharon Glaysher
Dennis Yiannakis
Francis G Gabriel
Penny Johnson
Marta E Polak
Louise A Knight
Zoe Goldthorpe
Katharine Peregrin
Mya Gyi
Paul Modi
Joe Rahamim
Mark E Smith
Khalid Amer
Bruce Addis
Matthew Poole
Ajit Narayanan
Tim J Gulliford
Peter E Andreotti
Ian A Cree
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-300

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