Killer genes in pancreatic cancer therapy

被引:7
作者
Fogar, P
Greco, E
Basso, D
Navaglia, F
Plebani, M
Pedrazzoli, S [1 ]
机构
[1] Univ Hosp Padova, Dept Med & Surg Sci, Padua, Italy
[2] Univ Hosp Padova, Dept Lab Med, Padua, Italy
关键词
pancreatic cancer; killer genes; cytotoxic bacterial toxins; viral and non-viral delivery systems;
D O I
10.1170/T598
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This review describes: 1. the main genetic alterations found in pancreatic cancer (EGF-R overexpression, SST-2 somatostatin receptor loss of expression, k-ras, p53 mutations and DPC4 mutations) and the effect of their replacements by gene therapy on tumor growth; 2. the use of suicide genes (HSV-TK and CD) for pancreatic cancer gene therapy in vitro and in vivo; 3. the implications for pancreatic cancer treatment when using cytotoxic bacterial toxins; 4. viral and non-viral delivery systems for the transfer of therapeutical genes into pancreatic cancer cells. Overall both the correction of pancreatic cancer cells main genetic alterations and the use of suicide genes allow only partial tumor regression in vitro and in vivo. The lack of a 100% effect for any studied strategy considered alone, indicates the need for combined therapies to achieve a satisfactory treatment of this tumor.
引用
收藏
页码:61 / 76
页数:16
相关论文
共 135 条
[1]   Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma [J].
Aguirre, AJ ;
Bardeesy, N ;
Sinha, M ;
Lopez, L ;
Tuveson, DA ;
Horner, J ;
Redston, MS ;
DePinho, RA .
GENES & DEVELOPMENT, 2003, 17 (24) :3112-3126
[2]   Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas [J].
Ammori, JB ;
Colletti, LM ;
Zalupski, MM ;
Eckhauser, FE ;
Greenson, JK ;
Dimick, Y ;
Lawrence, TS ;
McGinn, CY .
JOURNAL OF GASTROINTESTINAL SURGERY, 2003, 7 (06) :766-772
[3]  
Aoki K, 1997, MOL CARCINOGEN, V20, P251, DOI 10.1002/(SICI)1098-2744(199710)20:2<251::AID-MC12>3.3.CO
[4]  
2-P
[5]   Gene therapy for peritoneal dissemination of pancreatic cancer by liposome-mediated transfer of herpes simplex virus thymidine kinase gene [J].
Aoki, K ;
Yoshida, T ;
Matsumoto, N ;
Ide, H ;
Hosokawa, K ;
Sugimura, T ;
Terada, M .
HUMAN GENE THERAPY, 1997, 8 (09) :1105-1113
[6]   Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia [J].
Arteaga, CL .
SEMINARS IN ONCOLOGY, 2002, 29 (05) :3-9
[7]   Pancreatic cancer biology and genetics [J].
Bardeesy, N ;
DePinho, RA .
NATURE REVIEWS CANCER, 2002, 2 (12) :897-909
[8]   ANTISENSE OLIGONUCLEOTIDES DIRECTED AGAINST P53 HAVE ANTIPROLIFERATIVE EFFECTS UNRELATED TO EFFECTS ON P53 EXPRESSION [J].
BARTON, CM ;
LEMOINE, NR .
BRITISH JOURNAL OF CANCER, 1995, 71 (03) :429-437
[9]  
Bauerschmitz GJ, 2002, INT J ONCOL, V21, P1161
[10]   Overview of therapeutic vaccination approaches for cancer [J].
Berinstein, N .
SEMINARS IN ONCOLOGY, 2003, 30 (03) :1-8