1、 2012 5 18 ; 20(14): 1171-1177 ISSN 1009-3079 (print) ISSN 2219-2859 (online) EDITORIAL , . , . Progress in molecularly targeted therapy for cholangiocarcinoma Qin-Yu Li, Wei-Ze Wu, Tian-Quan Han, Sheng-Dao Zhang Qin-Yu Li, Wei-Ze Wu, Tian-Quan Han, Sheng-Dao Zhang, Department of Surgery, the Af l
2、iated Ruijin Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Institute of Digestive Surgery, Shanghai 200025, China Supported by: Shanghai Science Foundation, Medical Branch, No. 08411968000 Correspondence to: Wei-Ze Wu, Chief Physician, Depart- ment of Surgery, the Af liated Rui
3、jin Hospital, Shanghai Ji- aotong University School of Medicine; Shanghai Institute of Digestive Surgery, 197 Ruijin 2nd Road, Shanghai 200025, China. Received: 2011-08-03 Revised: 2012-03-22 Accepted: 2012-04-20 Published online: 2012-05-18 Abstract Cholangiocarcinoma (CC) is an uncommon tu- mor t
4、hat may arise anywhere from the biliary epithelium. Chinese CC patients account for more than 55% of CC cases in the world. Complete tumor resection has been recognized as the most effective therapy for CC. Unfortunately, only 10% of the patients are considered candidates for surgical resection. Lon
5、g-term survival remains poor in these patients, and the5-year survival rate is about 5%. Median survival of patients with the tumor unresectable is only a few months. Although standard systemic chemotherapy ap- proaches are emerging, the prognosis remains poor. Molecularly targeted therapies are a n
6、ew treatment for advanced CC. The results of recent clinical trials of targeted therapies for CC appear promising. This article will review the molecular basis for targeted therapies for CC and evaluate recent clinical trials on targeted agents. Key Words: Cholagiocarcinoma; Treatment; Mo- lecular t
7、arget Li QY, Wu WZ, Han TQ, Zhang SD. Progress in molecula- rly targeted therapy for cholangiocarcinoma. Shijie Huaren Xiaohua Zazhi 2012; 20(14): 1171-1177 , . , . , , 10% . 5 5%, 1 . . . . http:/ , , . 1979 1998 1.4-1.7/100 000 1 . (intrahepatic cholangiocarcino- ma, IHCC) (extrahe- patic cholangi
8、ocarcinoma, EHCC) 2 . IHCC , 3 , Blumgart Blechacz 4 5 IHCC , . Klatskin , , , 1172 ISSN 1009-3079 (print) ISSN 2219-2859 (online) , , 10% . 5 5%, 1 . . . Klatskin 1965 6 . EHCC 3 . , EHCC, EHCC 2 , EHCC , 3 7,8 . , 55% 3 . , . 9 ( Caroli ) 10 . , , , 3 . , IHCC , EHCC . , , . . , 11,12 , , , 10% ,
9、 7 . 5 ( ) 5% 13 . R0 64%-71%, 5 21%-30% 14 . 5 , 8 , 14 . 3-4 mo, ( ) 4-10 mo 15 . , 1 8,16 . (gemcitabi- ne) 5- , 8 . Eckel 16 1985-2006 , 1996-2006 (American society of clinical oncology, ASCO) , , 112 , 1 2 , 2 810 . ( )22.6%, ( )57.3%, 4.1 mo, 8.2 mo. 2009 ASCO , Valle 410 , , (8.0 mo vs 5.0 mo
10、), (11.7 mo vs 8.1 mo), 0.64. , 13 . 17 . , , 18 . , , , . . . (tyrosine kinase inhibitor, TKI) . (epidermal growth factor, EGF) (epidermal growth factor receptor, EGFR) (vascular endothelial growth factor receptor, VEGFR) (platelet-derived growth factor receptor, PDGFR) . , ; TKI 19 . , DNA , , 20
11、. , EGF (hepatocyte growth factor, HGF) 6 DNA 3 , . 2.1 EGFR (human epidermal growth factor receptor, HER) HER-1 HER-2 HER-3 HER-4, HER-1 EGFR ErbB-1 21 , , EGFR 22 . EGFR . EGFR TKI, EGFR , , . TKI 4 15 : (1) EGFR, erlotinib( , Tarceva) gefitinib( , Ir- 1173 essa); (2) EGFR HER-2, lapatinib( , Tyk
12、erb, GW572016); (3) 4 EGFR ; (4) EGFR VEGFR, vandetanib( ZACTIMA ZD6474) NVP- AEE788. vandetani , KRAS 23 . EGFR cetuximab( , Erbitux ) EGFR , , , , , . trastuzumab( , Herceptin ) HER-2 24 , . Panitumumab( Vectibix) , . 2.2 (vascular endothelial growth factor, VEGF) . VEGF , 6 , , , . , VEGF , . VEG
13、FR, . (platelet-derived growth factor. PDGF) , . Bevacizumab( , Avastin ) FDA VEGF , , VEGF, FLT-1 , . , . VEGF , , , . , . Sorafenib( BAY 43-9006, Nexavar) VEGF , VEGFR-2 VEGFR-3 PDGFR c-kit Raf/Mek/Erk 25 , , 26 . sunitinib( , Sutent) 27 . 2.3 c-kit Imatinib( , Gleevec) c-kit PDGFR . sunitinib, c-
14、kit VEGFR-1-3 PDGFR . Kamenz EHCC c-kit 37%(7/19 ), 2 , 5 28 . c-kit . 2.4 c-Met/HGF c-Met 7q, HGF , . HGF c-Met, , . c-Met 29 . Farazi 30 IHCC c-met 80% . c-Met , c-Met HGF , , AMG102 XL880 31 . 2.5 -2 -2(cyclo- oxygenase-2, COX-2) . COX-2 . COX-2 , 32 . COX-2 , E2(prostaglandin E2, PGE2) . . PGE2
15、EGFR, , COX-2 PGE2 . EGFR COX-2, COX-2 PGE2 EGFR . COX-1 COX-2, COX-2 SC-236 NS-398 cele- coxi 33 . 2.6 EGFR COX-2 ErbB2/HER-2 COX-2 33 . , 33 , EGFR 36.4% (mitogen- activated protein kinase, MAPK) 75.8% VEGF 57.6% COX-2 93.9%, EGFR MARK VEGF . , EGFR , MARK , EGFR (15 mo) (35 mo). EGFR COX-2 , EGFR
16、 COX-2 , COX-2/PGE2/EGFR 34 , erlotinib EGFR celecoxib COX-2 . (QBC939, FRH) , . Eckel 1985- 2006 , 1996-2006 (ASCO) , , 112 , 1 2 , 2 810 1174 ISSN 1009-3079 (print) ISSN 2219-2859 (online) , G 0 -G 1 . , EGFR MARK , VEGF . erlotinib celecoxib 35 . . , . 36 37 38 39 27 40 , 41 . EGFR (1991-2004 )
17、236 42 , IHCC 106 , EHCC 130 . IHCC EGFR VEGF HER-2 27.4% 53.8% 0.9%, EHCC 19.2% 59.2% 8.5%. EHCC EGFR , VEGF IHCC . EGFR IHCC , , 2.67, IHCC 1.89. EGFR , VEGF . . 3.1 EGFR EGFR(HER-1) erlotinib 43 42 ( ) , EGFR 81%. 7 (17%) 6 mo, 3 4 4 14 mo , 7.5 mo. 1-2 , 3 2-3 . erlotinib . Lubner 44 erlotinib VEGF bevacizumab 53 , 6 (12%) , 25 (51%) , 4.4 mo, 9.9 mo, EGFR 1 k-ras . erlotinib beva- cizumab . 2009 ASCO , Malka
