By systematically profiling expression of apoptosis pathway proteins with respect to histological sub-types of non-small cell lung cancer in human lung cancer cell lines, we have been able to identify specific patterns of defects in the expression and regulation of apoptosis pathways in lung cancer cells. Also, these apoptosis pathway differences between lung cancer cell types may suggest specific intra-cellular road-blocks which are critical to overcome in order to cause cell death in the lung cancer cell. To that effect, we have performed preliminary studies which show that knock-down of specific anti-apoptosis molecules can successfully render a previously apoptosis-inducing drug-resistant lung cancer cell more susceptible to such treatment and result in cancer cell death. Our next goals are to elucidate the mechanisms responsible for the differences in apoptosis expression in lung cancer sub-types and to perform additional validation studies using clinical relevant specimens.
