Drug screening and grouping by sensitivity with a panel of primary cultured cancer spheroids derived from endometrial cancer
In: Cancer Science, Jg. 107 (2016-03-16), S. 452-460
Online
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Zugriff:
Several molecular targeting drugs are being evaluated for endometrial cancer; selecting patients whose cancers are sensitive to these agents is of paramount importance. Previously, we developed the cancer tissue-originated spheroid method for primary cancer cells taken from patients' tumors as well as patient-derived xenografts. In this study, we successfully prepared and cultured cancer tissue-originated spheroids from endometrial cancers. Characteristics of the original tumors were well retained in cancer tissue-originated spheroids including morphology and expression of p53 or neuroendocrine markers. We screened 79 molecular targeting drugs using two cancer tissue-originated spheroid lines derived from endometrioid adenocarcinoma grade 3 and serous adenocarcinoma. Among several hits, we focused on everolimus, a mammalian target of rapamycin complex 1 inhibitor, and YM155, a survivin inhibitor. When sensitivity to everolimus or YM155 was assessed in 12 or 11 cancer tissue-originated spheroids, respectively, from different endometrial cancer patients, the sensitivity varied substantially. The cancer tissue-originated spheroids sensitive to everolimus showed remarkable suppression of proliferation. The phosphorylation status of the mammalian target of rapamycin complex 1 downstream molecules before and after everolimus treatment did not predict the effect of the drug. In contrast, the cancer tissue-originated spheroids sensitive to YM155 showed remarkable cell death. The effect of YM155 was also confirmed in vivo. The histological type correlated with YM155 sensitivity; non-endometrioid adenocarcinomas were sensitive and endometrioid adenocarcinomas were resistant. Non-canonical autophagic cell death was the most likely cause of cell death in a sensitive cancer tissue-originated spheroid. Thus, sensitivity assays using cancer tissue-originated spheroids from endometrial cancers may be useful for screening drugs and finding biomarkers.
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Drug screening and grouping by sensitivity with a panel of primary cultured cancer spheroids derived from endometrial cancer
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Autor/in / Beteiligte Person: | Endo, Hiroko ; Inoue, Masahiro ; Ueda, Yutaka ; Kimura, Toshihiro ; Yoshino, Kiyoshi ; Kamiura, Shoji ; Kimura, Tadashi ; Okuyama, Hiroaki ; Kubota, Satoshi ; Kiyohara, Yumiko |
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Zeitschrift: | Cancer Science, Jg. 107 (2016-03-16), S. 452-460 |
Veröffentlichung: | Wiley, 2016 |
Medientyp: | unknown |
ISSN: | 1349-7006 (print) ; 1347-9032 (print) |
DOI: | 10.1111/cas.12898 |
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