Abstract 2813: An interactome analysis for personalized chemotherapy using PDX/NOG models of non-small cell lung cancer
Authors: Chijiwa Tsuyoshi , Komura Daisuke , Haraguchi Mizuha , Noguchi Akira , Sato Hidemitsu , Ito Hiroaki , Nakayama Haruhiko , Katayama Makoto , Miyao Naoki , Matsui Naruaki , Tateishi Yuichi , Suemizu Hiroshi , Nakamura Yoshiyasu , Furukawa Daisuke , Isagawa Takayuki , Katoh Hiroto , Ishikawa Shumpei , Nakamura Masato , Miyagi Yohei 
Published: July 2017

Abstract
Lung cancer is one of the most common malignant diseases in the world, and its prognosis is generally poor. It is crucial to elucidate the biological mechanisms underlying lung cancer and accelerate the development of new treatment strategies. Xenografts derived from engrafting fresh surgical specimens directly into immunodeficient mice have recently enabled the development of more relevant in vivo models of human cancers. These patient-derived xenograft (PDX) models, established by the direct transfer of tumor tissue, retain similar morphologies, heterogeneities, and molecular signatures as the original cancers, and, thus, may be used in promising personalized medicine for cancer. We previously reported the rapid and efficient establishment of PDXs using super immunodeficient NOG mice (PDX/NOG model). In the present study, we analyzed the gene expression and cancer-stroma interaction profiles of PDXs established from NSCLC patients. We also discussed the possibility of individual PDX/NOG model simulations for personalized cancer chemotherapy. Ten NSCLC lines of PDX/NOG (Age 43-78 years; 8 men and 2 women; 7 adenocarcinoma, 1 adenosquamous carcinoma, 1 squamous carcinoma, and 1 large cell carcinoma) were presented. In these cases, clinical information regarding chemotherapy for donor patients was retrieved where possible. Genome sequencing and comprehensive analyses of tumor-stroma interactions (CAncer-STromal INteractome analysis, CASTIN) were performed on mRNA. CASTIN showed tumor-stroma interactions in PDX/NOG comprehensively and quantitatively at the gene expression level by distinguishing gene arrangements in human tissue (Cancer) from mouse tissue (Stroma) as signal strengths (ligand dependency (%) / receptor dependency (%)). Interactions of EGF(cancer)-EGFR(stroma) were observed from 1.2 (15%/0%) to 11.5 (94%/80%) as widely-distributed. Interactions of VEGFA(cancer)-KDR(stroma) were observed from 49.1 (31%/51%) to 301.7 (83%/100%) as closely-distributed. These interactions of EGF-EGFR or VEGFA-KDR in PDX/NOG closely reflected the clinical effectiveness of an EGFR inhibitor (Cetuximab) or VEGF-A inhibitor (Bevacizumab). The CASTIN results of PDX/NOG appear to be reliable for clinical simulations of chemotherapy and will definitely assist in the selection of the most sensitive anti-cancer drug. The fast and efficient establishment of individual PDXs will contribute to personalized anti-cancer therapies.
Citation Format: Tsuyoshi Chijiwa, Daisuke Komura, Mizuha Haraguchi, Akira Noguchi, Hidemitsu Sato, Hiroaki Ito, Haruhiko Nakayama, Makoto Katayama, Naoki Miyao, Naruaki Matsui, Yuichi Tateishi, Hiroshi Suemizu, Yoshiyasu Nakamura, Daisuke Furukawa, Takayuki Isagawa, Hiroto Katoh, Shumpei Ishikawa, Masato Nakamura, Yohei Miyagi. An interactome analysis for personalized chemotherapy using PDX/NOG models of non-small cell lung cancer [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 2813. doi:10.1158/1538-7445.AM2017-2813