Genomics-based screening of novel therapeutic targets and biomarkers for lung cancer.

Abstract

e15093 Background: Since the number of lung cancer patients who show objective response to standard treatments is still limited, development of new anti-cancer agents with minimum risk of side effects and specific cancer biomarkers is urgently required. Methods: We have been screening new therapeutic targets and their companion biomarkers for lung cancer as follows; i) To identify overexpressed genes in lung cancers by the gene expression profile analysis, ii) To verify the candidate genes for their scarce expression in normal tissues, iii) To validate the clinicopathological importance of their protein expression by tissue microarray covering hundreds of lung cancers, and iv) To characterize their function for the growth and/or survival of lung cancer cells by siRNAs. Results: We identified dozens of candidate oncoproteins and selected a lung cancer cell division-associated protein 1 (LCDAP1). Immunohistochemical analysis showed that LCDAP1 was expressed in 171 of 267 (64%) non-small cell lung cancer (NSCLC) tissues but not in normal lung epithelia. LCDAP1 expression was significantly associated with poor prognosis for NSCLC patients. To investigate its function, we screened LCDAP1-binding protein in lung cancer cells and found an interaction of LCDAP1 with a member of 5'-to-3' DNA helicase that was also up-regulated in lung cancer cells. Knockdown of either of LCDAP1 or its binding partner expression with siRNAs significantly inhibited the growth of cancer cells. Conclusions: Our genomics-based screening could be useful to develop diagnostic and prognostic biomarkers as well as therapeutic targets for small molecules, monoclonal antibodies, and nucleic acid drugs against lung cancer.