Abstract 5846: Comprehensive genomics-based screening of novel therapeutic targets and biomarkers for lung cancer

Abstract

Abstract As the number of patients with lung cancer who show good response to standard therapies is limited, new molecular targeted therapies and biotherapies with predictive biomarkers are urgently required. We have been developing molecular therapies targeting oncoproteins with their companion diagnostics as follows, i) To identify overexpressed genes in 120 lung cancers by gene expression microarray analysis of 27,648 genes, ii) To verify the candidate genes for their scarce expression in 23 normal organs, iii) To validate the clinicopathologic significance of their protein expression by tissue microarray covering hundreds of lung cancers including non-small cell lung cancers (NSCLCs), and iv) To examine whether they are important for the growth or invasion of cancer cells by using siRNAs and/or small molecule inhibitors. By this screening system, we identified dozens of candidate target molecules and selected a gene encoding protein with a GAP domain, LAPG1 (lung cancer-associated protein with Gap domain 1). Immunohistochemical analysis showed that LAPG1 expression was observed in 69.9% of lung cancers. Moreover positivity of LAPG1 expression was associated with poor prognosis for lung cancer patients. Knockdown of LAPG1 expression by siRNAs suppressed growth of lung cancer cells. Introduction of LAPG1 increased the invasive activity of mammalian cells, indicating that LAPG1 could be a prognostic biomarker and therapeutic target for lung cancers. Our comprehensive genomics-based screening might be useful to select the novel biomarkers and therapeutic targets for developing small molecules, antibodies, nucleic acid drugs, and immunotherapies against lung cancer. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Comprehensive genomics-based screening of novel therapeutic targets and biomarkers for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5846.