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Invest New Drugs. 2007 Oct;25(5):417-23. Epub 2007 May 30.

In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression.

Author information

1
Asklepios Klinik, St. Georg, Lohm├╝hlenstr. 5, 20099 Hamburg, Germany. hanauske.ind-synergen@t-online.de

Abstract

AIM OF THE STUDY:

mRNA expression of genes involved in the mechanism of action of pemetrexed was correlated with in vitro chemosensitivity of freshly explanted human tumor specimens.

EXPERIMENTAL DESIGN:

Chemosensitivity to pemetrexed was studied in soft-agar. Multiplex rtPCR experiments for reduced folate carrier (RFC), folate receptor-alpha (FR-alpha), folylpolyglutamate synthetase (FPGS), thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyl transferase (GARFT), mrp4, and mrp5 were performed in parallel. Correlations, threshold optimization, sensitivity, specificity, and efficiency were analyzed using the appropriate statistical methodologies.

RESULTS:

In 61 samples, low levels of TS, GARFT, DHFR, and mrp4 gene expression significantly correlated with chemosensitivity to pemetrexed. Optimization analyses demonstrated threshold values of 144 copies for TS and six copies for mrp4 relative to 10(4) copies of beta-actin.

CONCLUSIONS:

These results form a rational basis for the design of clinical trials to evaluate the expression of these enzymes as predictors for treatment outcome.

PMID:
17534577
DOI:
10.1007/s10637-007-9060-9
[Indexed for MEDLINE]
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