Abstract 3056: Combined disulfiram and radiation therapy against atypical teratoid/rhabdoid tumor

• Published in: Cancer research (Chicago, Ill.) Vol. 76; no. 14_Supplement; p. 3056
• Main Authors: Lee, Yeoung Eun, Choi, Seung Ah, Kwak, Pil Ae, Wang, Kyu-Chang, Phi, Ji Hoon, Lee, Ji Yeoun, Chong, Sangjoon, Moon, Youn Joo, Jangra, Anshika, Joo, Kyeung Min, Kim, Seung-Ki
• Format: Journal Article
• Language: English
• Published: 15.07.2016
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-3056

Abstract Disulfiram (DSF) has been studied as an anticancer drug and radiosensitizer. In our previous study, the therapeutic potential of DSF against atypical teratoid/rhabdoid tumor (AT/RT), one of the most aggressive forms of childhood cancer, had been confirmed using in vitro and in vivo studies. To develop more effective and safer therapy in AT/RT, we evaluated the sensitizing potential of DSF on radiation therapy (RT). The effect of DSF in low concentration alone and in combination with RT was investigated in vitro and vivo. Clonogenic assay, western blot analysis, autophagy assay and γ-H2AX foci staining were performed using several primary cultured AT/RT cells and cell lines. Also, in vivo study was performed using AT/RT orthotopic xenograft mouse model. Combination therapy with DSF and RT potently reduced clonogenicity and down-regulated protein expression of survivin and BCL2. The combination treatment strongly promoted the autophagic cell death and produced abundant γ-H2AX foci in all AT/RT cells. Moreover, the combination treatment significantly reduced the tumor growth and prolonged the survival rate compared to single treatment in AT/RT mouse model. Taken together, our results demonstrated that the combination therapy with DSF and RT has a synergistic therapeutic effect on AT/RT, suggesting a potential clinical application for AT/RT patients. Citation Format: Yeoung Eun Lee, Seung Ah Choi, Pil Ae Kwak, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Youn Joo Moon, Anshika Jangra, Kyeung Min Joo, Seung-Ki Kim. Combined disulfiram and radiation therapy against atypical teratoid/rhabdoid tumor. [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 3056.