Abstract 5195: Novel patient-derived xenograft and primary tissue culture cells for preclinical study in sarcoma

Abstract

Abstract Sarcomas are a group of malignant tumors displaying a wide diversity of pathological appearances and clinical responses due to the mesenchymal origin. Although certain sarcomas are characterized by the presence of unique fusion genes and mutations, the molecular backgrounds for tumorigenesis, metastasis, and resistance to treatments are remained to be further clarified in sarcomas. To improve clinical outcome, precise diagnosis followed by optimized therapy has long been desired in this field. Recently, clinical trials for application and re-localization of molecular targeting drugs have been conducted, and several drugs have been proven to effective in sarcomas. Preclinical models are indispensable to furthering our understanding of molecular background and facilitate novel therapeutic strategy. However, because of low prevalence the models are quite limited in sarcomas. To this end, we launched a project to establish patient-derived xenografts (PDXs) and primary culture cells of sarcomas. From April 2014 through October 2015, we implanted surgical tumor tissues from 76 sarcoma patients into highly immune-deficient NOG mice, and banked them after three passages. The identities of sarcomas were histologically confirmed by a certified pathologist, and the utility of PDXs were confirmed by re-growing them after storage in liquid nitrogen. 17 PDXs were prepared for preclinical study including myxofibrosarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, liposarcoma, leiomyosarcoma, osteosarcoma and clear cell sarcoma. Tissue cultures were also conducted by utilizing surgical specimens or PDXs. 158 sarcoma tissue samples were subjected to primary culture. Five immortalized cell lines, and 33 primary cultured cell lines with a minimum number of passages were established. The former includes leiomyosarcoma and undifferentiated pleomorphic sarcoma, and the latter includes additional 10 subtypes such as myxofibrosarcoma, malignant peripheral nerve sheath tumor, liposarcoma, osteosarcoma, clear cell sarcoma, etc. Moreover, the molecular backgrounds of the established sarcoma PDXs and tissue cultured cells were evaluated by targeted sequencing using an original cancer gene panel (NCC oncopanel), which can detect targetable mutations and gene fusions. Clinical and pathological observations of the donor patients will be linked to the characters of PDXs and tissue cultures. The applications of these in vivo and in vitro models for preclinical study will be our next challenge. Citation Format: Xiaoqing Pan, Mami Takahashi, Hitoshi Ichikawa, Akihiko Yoshida, Akira Kawai, Toshio Imai, Tadashi Kondo. Novel patient-derived xenograft and primary tissue culture cells for preclinical study in sarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5195.