Abstract 4895: CT20p as a therapeutic for lung cancer with elevated chaperoning containing TCP1 (CCT) expression levels

Abstract

Abstract Lung cancer is the leading cause of cancer related fatalities worldwide and although there is a substantial effort in the development of improved, more specific, and less debilitating therapies, very little progress has been made accomplishing this goal. We propose the use of CT20p, a therapeutic peptide developed by our laboratory, as novel therapy for lung cancer. We have previously demonstrated that CT20p has tumor specific cytotoxicity in breast cancer cells and it induces tumor regression in xenograft models of breast cancer. We have also determined Chaperonin containing T-complex (CCT) to be the intracellular target of CT20p and that susceptibility to CT20p correlates with its expression levels, with tumor cells expressing high levels of CCT being the most susceptible. CCT is a large macromolecular complex composed of 8 subunits (CCTα, CCTβ, CCTγ, CCTδ, CCTϵ, CCTζ, CCTη, CCTθ). Immunoblot probing against four relevant CCT subunits (CCTβ, CCTγ, CCTδ, CCTϵ) was used to determine their relative expression level in five small cell lung cancer (SCLC) cell lines when compared to normal lung cells. We determined that the expression levels of the four probed CCT subunits varied amongst the five SCLC cell lines, however, the four CCT subunits were always expressed at higher levels when compared to normal lung cells. Immunohistochemistry staining for CCTβ was used on tissue microarray (TMA) of lung cancer progression. Results were interpreted on a scale of 1 to 4 (with 4 being the strongest staining). We determined that CCTβ levels increase with cancer severity and identified a significant correlation between CCTβ levels and cancer progression in both small cell lung carcinoma (SCLC) and Squamous cell lung carcinoma (SqCLC). Using The Cancer Genome Atlas (TCGA) database, we have found CCT gene alterations in clinical lung cancer cases range from 10% to 43%, however, only CCT4 gene amplification in SqCLC cases correlated with decreased survival. Altogether, these results suggest that CT20p has the potential for being a therapeutic for multiple types of lung cancer due to increased target expression. Citation Format: Ana C. Carr, Amr S. Khaled, Rania Bassiouni, Annette R. Khaled. CT20p as a therapeutic for lung cancer with elevated chaperoning containing TCP1 (CCT) expression levels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4895. doi:10.1158/1538-7445.AM2017-4895