Inhibition of the met receptor in mesothelioma.

Background: Expression of the Met receptor and its ligand, hepatocyte growth factor (HGF), has been observed in 74% to 100% and 40% to 85% of malignant pleural mesothelioma (MPM) specimens, respectively. HGF stimulation has been shown to enhance MPM cell proliferation, migration, cell scattering, and invasiveness.

Experimental Design: To investigate a potential therapeutic role for the Met receptor in MPM, we examined the effects of PHA-665752, a specific small-molecule inhibitor of the Met receptor tyrosine kinase, in a panel of 10 MPM cell lines.

Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare malignancy with no known curative modality. Approximately 70% of MPMs have high levels of expression of the epidermal growth factor receptor (EGFR), and a subset of cell lines derived from MPM patients express both EGFR and transforming growth factor alpha, suggesting an autocrine role for EGFR in MPM. We have determined the effects of EGFR inhibition in MPM cell lines in vitro, using four MPM cell lines derived from previously untreated patients with epithelial (H2461 and H2591), sarcomatoid (H2373), and biphasic (MSTO-211H) MPM.