Pemetrexed: Target gene expression in human solid tumors correlates with chemosensitivity patterns.

3128 Background: The novel antifolate ALIMTA (pemetrexed) exhibits clinical activity in a variety of solid tumors. Primary targets comprise thymidilate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). In the present study, target gene expressions were correlated with in vitro chemosensitivity of freshly explanted human tumor specimens. Such correlations in tumors taken directly from patients may help to rationally design subsequent clinical trials. Methods: Freshly biopsied tumor cells (solid tumors, pleural effusions, or ascites) were used for soft-agar cell cloning experiments. Cells were exposed to various concentrations of ALIMTA and clonogenic tumor growth was evaluated. Another part of the tumor specimens was shock frozen immediately after removal. Messenger RNA was isolated and reversely transcribed to cDNA followed by real-time multiplex PCR experiments. Results from these gene expression experiments were normalized against β-actin transcript...