Abstract 1438: Targeting metabolic enzyme with locked nucleic acids in non-small cell lung cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Despite advances in our knowledge of genetics of cancer and some progress in cancer treatment over the last few decades, lung cancer remains the leading cause of cancer mortality worldwide. Recently cancer metabolomics have been widely applied into cancer research, including of cancer diagnosis and therapy. Our recent work has identified tumor initiating cells (TICs) derived from non-small cell lung cancer (NSCLC) patients and shown that metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in NSCLC. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients. Those findings provide potential diagnostic markers and/or therapeutic target for NSCLC. Locked nucleic acids (LNAs) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. In this study we tested NSCLC patient-derived xenograft tumor growth inhibition by GLDC LNAs antisense oligonucleotides. These LNAs antisense oligonucleotides strongly reduce GLDC protein levels. The osmotic minipumps were filled with GLDC LNAs antisense oligonucleotides at 0.5,1 and 5 mg/kg/day dose and implanted dorsally into tumor-bearing NOD/SCID Il2rγ-/- mice. Tumor growth was inhibited at dosages from 1 mg/kg/day. LNAs antisense oligonucleotides appeared to be non-toxic at dosages of 5 mg/kg/day. Furthermore, we found significant changes of serum metabolomics in lung cancer patients compared to normal donors. Our data show that GLDC LNAs antisense oligonucleotides are potent genotype-specific drugs that can inhibit lung tumor growth in vivo. Note: This abstract was not presented at the meeting. Citation Format: Wen Cai Zhang, Bing Lim. Targeting metabolic enzyme with locked nucleic acids in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1438. doi:10.1158/1538-7445.AM2014-1438