Abstract 1355: Utility of primary cultured cells in personalized chemotherapy for angiosarcoma of the oral cavity
Authors: Tomohiro Hamakawa, Koh-ichi Nakashiro, Hiroshi Tanaka, Hiroyuki Goda, Satoshi Hino, Hiroyuki Hamakawa
Journal: Cancer Research (2012)

Abstract Current treatments for major malignant tumors are based on evidences accumulated over the world and clinical trials with molecular target drugs that are expected to improve their prognosis are ongoing. In contrast, rare malignant tumors have no standard therapies and few evidences for effective drugs. Moreover, epidemiology, etiology, pathogenesis and molecular mechanisms are unknown because published data are based on a few case series and experimental materials can be used in vitro do not exist. Thus we have to manage a treatment case by case when facing a rare tumor. One of the useful methods to evaluate drug efficacy is the collagen gel droplet embedded culture drug sensitivity test (CD-DST), but a resected tumor tissue as an examination materials is limited. Primary cultured cells are thought to be an alternative material for various analyses. Angiosarcoma is a rare soft-tissue sarcoma of endothelial cell origin showing a poor prognosis. A 72-year-old man who has large masses on upper and lower gingiva came to our department and a palliative excision was performed. He also had multiple nodules in both lungs and cervical lymph nodes. Histopathological diagnosis was angiosarcoma because the immunohistochemical stainings showed that vimentin, CD31 and vW factor were positive. We attempted to culture the excised tumor specimen in vitro and obtained primary cultured cells with stable proliferation, and confirmed their in vivo tumorigenicity in athymic nude mice. First, both primary tumor tissues and cultured cells were assessed their sensitivity against 8 anti-tumor drugs by CD-DST. We evaluated their growth inhibitory effects as the ratio of total volume of colonies in the treated group to that in the untreated group (T/C%). The most effective drug, gemcitabine, had 20.9 T/C% in tumor tissues and 35.4 T/C% in cultured cells, and the second, docetaxel, had 32.2 T/C% and 40.2 T/C%, respectively. The other drugs showed the similar sensitivity between both types of samples. Next, we determined the gene expression profiles of both samples and a normal gingival tissue by microarray analysis. The data showed that 2,498 genes in primary tumor tissues and 2,893 genes in primary cultured cells had more than 5-fold change compared to control. Of these, 1,627 genes were common, and then we found the overexpression of 170 cancer-related genes including Aurora kinase A (AURKA) among these genes. Finally, we investigated the effect of a selective AURKA inhibitor MLN8237 on the growth of primary cultured angiosarcoma cells in vitro, and then observed the growth inhibitory effect of MLN8237 against these cells. These results suggest that primary cultured tumor cells may be useful for predicting the efficacies of various anti-tumor drugs and developing novel therapeutic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1355. doi:1538-7445.AM2012-1355