Abstract LBA043: mRNA expression of mTOR signaling components as potential predictive biomarker in pancreatic neuroendocrine neoplasms

Abstract

Abstract Medical therapeutic options for the treatment of well-differentiated pancreatic neuroendocrine neoplasms (pNENs) include the mTOR pathway inhibitor everolimus (in combination with 5-Fluorouracil). Criteria to assess prognosis in pNEN patients are still limited, as biomarkers to predict the therapeutic response are still unknown. Several studies could show aberrant mTOR signaling pathway activity at different levels of the signaling cascade in pNENs. In this study, we analyzed the mRNA expression of different mTOR pathway components in well-differentiated pNENs, in order to identify potential prognostic and predictive biomarkers. In this retrospective multicenter study, real-time quantitative TaqMan reverse transcriptase-polymerase chain reaction was used to analyze mRNA expression of eleven different mTOR pathway genes (IGF-1, IGFBP-3, PIK3CA, AKT-1, MTOR, MLST8, DEPTOR, RAPTOR, RICTOR, 4EBP1 und VEGF-A), in tumor tissue of 75 patients with well-differentiated pNENs in comparison to normal pancreatic tissue. Relative gene expression was determined according to the 40-ΔCT method using CALM2 as housekeeping gene. The analysis of mRNA expression levels of the aforementioned eleven genes indicated an increased mTOR signaling activity in pNENs. A distinct linear correlation only occurred between MTOR and AKT-1. Clear association between mRNA expression and a clinical feature was only found for RAPTOR: High RAPTOR mRNA expression was significantly correlated with better overall survival in unselected patients. No prediction to everolimus treatment response could be deduced by mRNA expression analysis in a small subgroup of 21 patients. Even though mRNA expression of different mTOR pathway components indicated an enhanced activity of this signaling cascade in tumor tissue of pNEN patients, we could not identify a statistical significant parameter useful for prediction of everolimus treatment response. The predictive value of this study is limited due to the low number of patients who received treatment with everolimus. Further prospective studies analyzing the predictive value of the expression of mTOR pathway genes are desirable. Citation Format: Sebastian Wolfshöfer, Adrian C Lock, Daniel Kaemmerer, Ralph M Wirtz, Franziska Briest, Sven P Haugvik, Malte Buchholz, Anja Rinke, Ruza Arsenic, Marianne Pavel, Dieter Hörsch, Arend Koch, Patricia Grabowski. mRNA expression of mTOR signaling components as potential predictive biomarker in pancreatic neuroendocrine neoplasms [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA043.