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

Sharon Glaysher1, Dennis Yiannakis, Francis G Gabriel

  • 1Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK. sharonglaysher@googlemail.com

BMC Cancer
|August 29, 2009
PubMed
Abstract

Insights

Molecular signatures in non-small cell lung cancer (NSCLC) predict chemotherapy response. Gene expression patterns correlate with in vitro chemosensitivity, paving the way for personalized lung cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacogenomics

Background:

  • Non-small cell lung cancer (NSCLC) displays significant variability in chemotherapy response.
  • This heterogeneity is mirrored in in vitro models, suggesting underlying molecular mechanisms.
  • This study investigated if known drug resistance mechanisms explain NSCLC chemosensitivity in vitro.

Purpose of the Study:

  • To test the hypothesis that inherent tumor resistance mechanisms dictate NSCLC chemosensitivity.
  • To correlate in vitro chemosensitivity data with quantitative gene expression of resistance markers.
  • To explore the potential for developing predictive gene signatures for individualized lung cancer chemotherapy.

Main Methods:

  • Assessed chemosensitivity of 49 NSCLC tumors using the ATP-based tumor chemosensitivity assay (ATP-TCA).
  • Quantified expression of resistance genes via RT-PCR in a Taqman Array using RNA from FFPE tissues.
  • Compared ATP-TCA results with gene expression data to identify correlations.

Main Results:

  • Observed significant heterogeneity in tumor chemosensitivity.
  • Found strong correlations between multi-gene signatures and the activity of single agents and combinations, rather than individual gene expression.
  • Docetaxel activity linked to drug pump expression; cisplatin activity to DNA repair enzyme expression.
  • Apoptotic gene expression strongly influenced the activity of both docetaxel and cisplatin.
  • Combination therapies showed gene expression signatures reflecting resistance mechanisms of both agents.

Conclusions:

  • Genes involved in drug sensitivity and resistance mechanisms correlate with in vitro chemosensitivity.
  • Identified potential for predictive gene signatures to guide personalized chemotherapy in NSCLC.
  • Molecular profiling may enhance individualized treatment strategies for lung cancer patients.