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学术讲座:Repurposing diabetes drug phenformin for cancer treatment

更新时间: 2018-07-05 点击量: 243
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一、主题:Repurposing diabetes drug phenformin for cancer treatment

二、主讲人:哈佛大学医学院 副教授 郑斌

三、时间:2018年7月9日(周一)  下午16:00-18:00

四、地点:清水河校区宾诺咖啡   

五、主持人:医学院副院长 牟雁东

六、内容简介:

        Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated anti-tumor activity both in vitro and in vivo. The energy-sensing AMP-activated protein kinase (AMPK) is known to be a major cellular target of biguanides. Based on our discovery of crosstalk between the AMPK and BRAF signaling pathways, we investigated the anti-tumor effects of combining phenformin with a BRAF inhibitor PLX4720 on the proliferation of BRAF mutated melanoma cells in vitro and on BRAF-driven tumor growth in vivo. Co-treatment of BRAF mutated melanoma cell lines with phenformin and PLX4720 resulted in synergistic inhibition of cell viability, compared to the effects of the single agent alone.

More recently, we have also investigated potential effects of biguanides on the tumor microenvironment. We found that phenformin selectively inhibited granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Our findings demonstrate a selective, inhibitory effect of phenformin on G-MDSCs-driven immune suppression and provide a rational basis for future clinical evaluation of phenformin/anti-PD-1 combination therapy.

七、主讲人简介:

        郑斌,博士,现任哈佛大学医学院副教授麻省总医院助理研究员。于加州大学圣地亚哥分校获得博士学位(导师为美国科学院和美国人文与科学学院院士 Marilyn Gist Farquhar教授)

        郑斌博士致力于黑色素瘤中代谢分子的机理研究,发现BRAF可以作为AMPK的底物,阐释了AMPK与BRAF通路之间的调控机制,并发现AMPK的激活剂苯乙双胍可以增强BRAF靶向治疗的抗肿瘤作用,相关研究已进入Ⅰ期临床试验。他的研究成果先后在 science, Nature medicine, PNAS, Molecular cell等国际上知名杂志发表,SCI收录论文30多篇。现担任J. Investigative Dermatology助理编辑, Nature Medicine,  Nature Cell Biology,  Cancer Discovery、J. Clinical Oncology等多种国际知名期刊的评委。