Abstract B38: Clinical applications of PDX/NOG models for personalized chemotherapy – possible use in chemo-sensitivity testing and clinical sequencing

• Published in: Clinical cancer research 2016-08, Vol.22 (16_Supplement), p.B38-B38
• Main Authors: Chijiwa, Tsuyoshi, Isagawa, Takayuki, Noguchi, Akira, Sato, Hidemitsu, Hayashi, Akimune, Cho, Haruhiko, Shiozawa, Manabu, Kishida, Takeshi, Morinaga, Soichiro, Yokose, Tomoyuki, Katayama, Makoto, Takenaka, Nobuo, Haraguchi, Mizuha, Miyao, Naoki, Tateishi, Yuichi, Kawai, Kenji, Suemizu, Hiroshi, Yamada, Roppei, Nakamura, Yoshiyasu, Imai, Kohzoh, Komura, Daisuke, Ishikawa, Shumpei, Nakamura, Masato, Miyagi, Yohei
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1557-3265.PDX16-B38

Personalized medicine represents an ideal medical approach for cancer therapy. In the field of clinical oncology, personalized medicine or therapy involves the evolutionary expansion of conventional clinical approaches that progress from patient evaluation, differential diagnosis, to the treatment of diseases. A number of the complex techniques employed in personalized medicine, such as clinical genome sequencing, biochemical marker analyses, chemo-sensitivity testing, and cancer immunotherapy, require fresh, viable, and sufficient amounts of specimens for reliable estimations. Mice bearing patient-derived xenografts (PDXs) with clinical information (so-called “Cancer Xenopatients”) are remarkable systems in personalized medicine for cancer. We previously reported the rapid and efficient establishment of PDXs using NOG mice (PDX/NOG models, AACR2015 #1940, IJO 47 61-70 2015). NOG mice, NOD/Shi-scid/IL2Rγnull (NOG) mice derived from NOD/SCID mice with a common gamma chain, have multifunctional defects in natural killer cell activity, macrophage function, complement activity, and dendritic cell function in addition to the absence of functional T and B lymphocytes. NOG mice have been identified as the most appropriate immunodeficient host animal for the direct xenografting of fresh tumor tissue due to the preservation of cancer stem cells (CSCs). Fresh and valuable xenograft samples, similar to surgical samples with the preservation of CSC, are stably provided using PDX/NOG models. Moreover, human tissue (tumor) and mouse tissue (stroma) are clearly distinguished by immunohistochemical analysis or gene arrangement sequencing. In the present study, we discussed the possibility of using PDX/NOG model simulations for personalized cancer chemotherapy. We previously established 47 lines of gastrointestinal cancer xenografts. In these cases, clinical information regarding chemotherapy for donor patients was retrieved where possible. Collagen gel droplet-embedded culture-drug sensitivity tests (CD-DST) were performed on 16 lines of PDX/NOG. In 4 of these lines, CD-DST were successfully conducted on original surgical specimens. The results of CD-DST between original and PDX/NOG specimens generally correlated (R2=0.01-0.89). The results of CD-DST using PDX/NOG specimens were compatible with the clinical effects of anti-cancer drugs. Genome sequencing and interactome analyses, a comprehensive analysis of tumor-stroma interactions innovated by Professor Ishikawa S. at T