1、2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.The development of new therapeutic strategies for esophageal squamous cell carcinoma 李 騫 2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.（Self-introduction）The Fourth Hospital of Hebei Medical University Shijiazhuang Cit
2、y,Hebei Province,China Department of Thoracic Surgery Since its foundation,the department of thoracic and cardiac surgery has performed more than 33000 surgeries on esophageal and cardiac cancer,the most in the world,and leads the world in the diagnosis and curative effect of esophageal cancer.The d
3、epartment has 4 wards,more than 160 beds and 39 doctors,including 11 chief physicians,9 associate senior physicians,8 attending physicians and 11 resident physicians.119 101 51 15 16 The Operations in 2016 Jan-June Lang cancerEsophageal cancerGastric cancerMediastinal surgeryOthers2016.10.29 千葉大学先端応
4、用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Background 2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Squamous cell carcinoma of the esophagus is one of the cancer that has poor prognosis of malignancy,and the 5-year survival rate less than 42.4%1)。the median survival of the patie
5、nt of unresectable esophageal cancer is shorter,which only in 9.2 months that compared with stomach cancer and colon cancer 2)。（Backgroud）1)全協加盟施設生存率協同調査 2004-2007年症例 2)Iizuka et al.J Clin Oncol.1992 2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.That response rate of 5FU-cisplatin
6、therapy,which is the current standard chemotherapy is not satisfactory and only about 35.9%3)For esophageal cancer,There are only 5 types of anticancer drug in insurance listed,(except MMC,VDS)That has not yet been the insurance approval of targeted therapy for esophageal cancer in Japan So that it
7、is necessary for developing some novel treatments to improve this situation.3)Iizuka et al.J Clin Oncol.1992 2016.10.29 千葉大学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.A Epigenetic therapy ：Classification based on the epigenetic state ：Classification of G0 Phase B The treatment target about HPV
8、-associated ESCC Whether exists the epigenetic driver mutation.The silence phase can be changed at the epigenetic therapy 2016.10.29 千葉大学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.A Epigenetic therapy ：Classification based on the epigenetic state ：Classification of G0 Phase B The treatment tar
9、get about HPV-associated ESCC 2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Histone DNA The DNA is surrounding the Histone 1.65times。（Chromatin structure）2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.簡単言、蛋白 DNA Genetics Gene expression is defined in the base seque
10、nce of DNA.Histone 2016.10.29 千葉大学先端応用外科 土曜日朝会 Dept.of Frontier Surgery,Chiba Univ.蛋白 DNA The gene expression is active or not,it is not depend on the nucleotide sequence of the DNA Ac Ac Ac Ac Me Me Me Me Me Ac Ac Ac Acetylation of histone proteins(),methylation of DNA()Ac Me Histone 2016.10.29 千葉大
11、学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Epigenetic therapy 治療 The development of therapeutic drugs have made great progress for abnormal epigenetic.The DNA methylation inhibitor and the histone deacetylate inhibitor is clinically applied to hematologic malignancies nowadays.2016.10.29 千葉大学
12、先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.The Normal Cell 2016.10.29 千葉大学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Genes that are not activated(Silencing)Histone acetylation enzyme Genes that are activated Genes that are not activated Ac Ac Ac Histone acetylation enzyme Genes that are
13、activated Genes that are inactivated Ac Ac Ac Histone acetylation enzyme Genes that are not activated Histone deacetylation Ac Ac Ac Genes that are activated The Cancer Cell Ac Ac Ac Inactivation of tumor suppressor gene Histone deacetylation Genes that are activated Genes that are inactivated Histo
14、ne Deacetylase inhibitor(HDAC inhibitor)Ac Ac Ac Inactivation of tumor suppressor gene Histone deacetylation Genes that are activated Genes that are inactivated Histone Deacetylase inhibitor(HDAC inhibitor)ACTIVE THE TSG Histone deacetylase inhibitors have been approved by USFDA BRAND Disease 2006 v
15、orinostat Zolinza Cutaneous T-cell lymphoma 2009 romidepsin Istodax Cutaneous T-cell lymphoma 2014 berinostat Beleodaq Peripheral blood T-cell lymphoma 2015 panobinostat Farydak Multiple myeloma curative effect 2016.10.29 千葉大学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Epigenetic therapy 治療 It
16、has a completely different mechanism of action,compare with anti-cancer drug of DNA cytotoxic such like cisplatin.Although it is expected that more effective against to the solid cancer,it is hard to say that has the sufficient effect yet due to clinical research.2016.10.29 千葉大学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Epigenetic therapy New treatment strategy is required.2016.10.29 千葉大学先端応用外科 水曜日朝会 Dept.of Frontier Surgery,Chiba Univ.Epigenetic therapy The existing anti-cancer drugs need