演題詳細

一般口演 / Oral Session

【E】一般口演 19 (Oral Session 19) :AML:Mechanism of Therapeutic Agent

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日程
2013年10月11日(金)
時間
14:25 - 15:25
会場
第4会場 / Room No.4 (さっぽろ芸文館 3F 黎明)
座長・司会
小林 正夫 (Masao Kobayashi):1
1:Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University, Japan
 
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A novel STAT inhibitor, OPB-31121, has a significant anti-tumor effect on STAT-dependent leukemia

演題番号 : OS-1-95

早川 文彦 (Fumihiko Hayakawa):1、杉本 慶樹 (Keiki Sugimoto):2,3、倉橋 信悟 (Shingo Kurahashi):4、直江 知樹 (Tomoki Naoe):5

1:Nagoya Univ. Hosp., Dept. Hematology, Nagoya, Japan、2:Nagoya Univ. Dept. Hematology and Oncology, Nagoya, Japan、3:Fujii Memorial Res. Ins., Otsuka Pharma. Co. Ltd., Otsu, Japan、4:Nagoya First Red Cross Hosp., Dept. Hematology, Nagoya, Japan、5:Nagoya Medical Center, Nagoya, Japan

 

Signal Transduction and Activator of Transcription (STAT) proteins are extracellular ligand-responsive transcription factors that mediate cell proliferation, apoptosis, differentiation, development, and immune response. Aberrant signal of STAT induces uncontrolled cell proliferation and apoptosis resistance and is strongly involved in cancer. STAT has been identified as a promising target for anti-tumor drug, but to date most trials were not successful. Here, we demonstrated that a novel STAT inhibitor, OPB-31121, strongly inhibited STAT3 and STAT5 phosphorylation without upstream kinase inhibition, and induced significant growth inhibition in various hematopoietic malignant cells. Investigation among various cell lines indicated that OPB-31121 is particularly effective on multiple myeloma, Burkitt lymphoma and leukemia cells harboring BCR-ABL, FLT3/ITD and JAK2 V617F, oncogenic kinases depended their oncogenicities on STAT3/5. Using immunodeficient mice transplantation system, we also showed the significant anti-tumor effect of OPB-31121 on primary human leukemia cells harboring those aberrant kinases and the safety on normal human cord blood. Finally, we demonstrated the model of overcoming the drug resistance to upstream kinase inhibitors with STAT inhibitor. These results suggested that OPB-31121 was a promissing anti-tumor drug. OPB-31121 is under phase I/II trial in Japan.

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