Molecular approaches to prevention and therapy of aerodigestive tract cancers.

We describe studies defining several molecular events in human non-small-cell lung cancer (NSCLC). These include increased growth factor and growth factor receptor expression and oncogene alterations. The epidermal growth factor receptor (EGFR) and erbB2 are expressed by NSCLC cells. Transforming growth factor-alpha (TGF-alpha) is produced by NSCLC and may mediate autocrine growth stimulation. Specific inhibition of K-ras oncogene expression by an antisense K-ras construct reduces the growth rate and tumorigenicity of NSCLC cells. Studies with antisense p53 in NSCLC with a homozygous p53 mutation suggest that the presence of the mutant form contributes to the transformed state.