Trial Information

Detection of Epithelial Growth Factor Receptor (EGFR) Mutation in Malignant Pleural Effusion of Lung Cancer Patients and Cancer Cell Lines Establishment

Lung cancer is the leading cause of mortality in the world. Previous study has shown that
about 88% lung cancer cases belong to non-small cell lung cancer (NSCLC) in Taiwan (1).
Approximately 50~90% of NSCLC patients had expression (or described as overexpression) of
EGFR in cancer (2,3). Although targeting the EGFR kinase domain using the inhibitors
gefitinib (Iressa) and erlotinib (Tarceva) has no effect against solid tumors, it achieves
impressive response in subgroup of NSCLC especially in Asian ethnic background, female sex,
the absence of a history of smoking, and a tumor with histologic feature of adenocarcinoma
(3,4,5). Molecular studies of highly responsive cases revealed high percentage of somatic
mutation within the tyrosine kinase, ATP-binding domain of the EGFR gene (6). One possible
explanation for this phenomenon is that the cancer cells are "addicted" to signaling via the
mutant EGFRs and die when the mutant oncoprotein is inactivated (7). However, specific
mechanisms underlying epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) induced
cell death have not been well delineated (7).

Approximately 90% of mutations affect a few specific amino acids. In-frame deletions in exon
19 centered on codons 756 to 750 make up 45~50% of mutations, and another 35~45% consist of
the missense mutation leucine to arginine at codon 858 (L858R) in exon 21 (8, 9, 10). The
link between EGFR-TKI response and EGFR mutations have been confirmed, but the increased
prevalence of mutations in Asian (25%to 50%) compared with North American and Western
European patients (10%) is currently unexplained (6,8-12). The response rate to TKI
treatment in mutations-positive is 77% (30% to 100% with most series >60%) compared with 10%
in mutation-negative cases (6). It is interesting that exon 19 deletion have increased
response and survival with TKIs compared with L858R cases (10, 13, 14). This is in contrast
to the natural history of patients, where those with exon 19 deletions appear to have
shorter survival than those with L858R (8). The biological difference is still unknown and
different mutations may have different biochemical signaling properties (15).

In this study, we will collect the pleural effusion from lung cancer patients. We will
characterize the EGFR status of the cancer cell from malignant pleural effusion and try to
establish the cancer cell lines from these patients. We hope to establish several cell lines
with different mutations and then we can compare the difference responses and signal
pathways in these cell lines. We can also explore the detailed mechanism of TKI responsive
cancer cell and try to develop other agent to enhance the pathways.