Apoptosis pathways as promising targets for skin cancer therapy

被引:57
作者
Eberle, J. [1 ]
Fecker, L. F. [1 ]
Forschner, T. [1 ]
Ulrich, C. [1 ]
Roewert-Huber, J. [1 ]
Stockfleth, E. [1 ]
机构
[1] Univ Hosp Berlin, Charite, Skin Canc Ctr, Dept Dermatol, Berlin, Germany
关键词
apoptosis; Bcl-2; COX-2; skin cancer; TRAIL;
D O I
10.1111/j.1365-2133.2007.07855.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Apoptosis pathways provide efficient safeguard mechanisms against cancer that are mediated via cell-intrinsic responses and immune-mediated extrinsic signals. Intrinsic pro-apoptotic pathways are largely controlled by p53 and Bcl-2 proteins, whereas the extrinsic induction of apoptosis is initiated by death ligands, such as tumour necrosis factor-alpha (TNF-alpha), CD95L/FasL and TNF-related apoptosis-inducing ligand (TRAIL), or by granzyme B. Initiation of these pathways results in the induction of a caspase cascade leading to cell death. The inactivation of pro-apoptotic pathways is elementary for tumourigenesis and may be responsible for therapy resistance. Thus, apoptosis-based strategies represent important tools for the development of effective tumour therapies. The aim of these therapies is to restore p53 activity, downregulate anti-apoptotic Bcl-2 proteins or NF-kappa B activity, and to upregulate extrinsic, death receptor-mediated pathways. The initial results of apoptosis-based strategies are proving promising. Also, topical treatments for actinic keratosis (AK), such as cyclo-oxygenase-2 inhibitors (e.g. diclofenac 3% gel), have been shown to trigger pro-apoptotic pathways. There is hope that pro-apoptotic strategies will lead to pronounced therapeutic success against skin cancer. Importantly, the involvement of the different pro-apoptotic pathways in specific tumour types needs to be unravelled and understood in order to evaluate drug effectiveness, as well as to modify and optimise therapeutic approaches.
引用
收藏
页码:18 / 24
页数:7
相关论文
共 61 条
[1]   The epidemiology of UV induced skin cancer [J].
Armstrong, BK ;
Kricker, A .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2001, 63 (1-3) :8-18
[2]   P53: An ubiquitous target of anticancer drugs [J].
Blagosklonny, MV .
INTERNATIONAL JOURNAL OF CANCER, 2002, 98 (02) :161-166
[3]  
Bocchia M, 2000, HAEMATOLOGICA, V85, P1172
[4]  
Bolshakov S, 2003, CLIN CANCER RES, V9, P228
[5]   A nonreplicating adenoviral vector that contains the wild-type p53 transgene combined with chemotherapy for primary breast cancer -: Safety efficacy, and biologic activity of a novel gene-therapy approach [J].
Cristofanilli, Massimo ;
Krishnamurthy, Savitri ;
Guerra, Laura ;
Broglio, Kristine ;
Arun, Banu ;
Booser, Daniel J. ;
Menander, Kerstin ;
Van Wart Hood, Jill ;
Valero, Vicente ;
Hortobagyi, Gabriel N. .
CANCER, 2006, 107 (05) :935-944
[6]   Guardians of cell death:: the Bcl-2 family proteins [J].
Daniel, PT ;
Schulze-Osthoff, K ;
Belka, C ;
Güner, D .
PROGRAMMED CELL DEATH, 2003, 39 :73-88
[7]   The kiss of death: promises and failures of death receptors and ligands in cancer therapy [J].
Daniel, PT ;
Wieder, T ;
Sturm, I ;
Schulze-Osthoff, K .
LEUKEMIA, 2001, 15 (07) :1022-1032
[8]   The role of UV induced lesions in skin carcinogenesis: an overview of oncogene and tumor suppressor gene modifications in xeroderma pigmentosum skin tumors [J].
Daya-Grosjean, L ;
Sarasin, A .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2005, 571 (1-2) :43-56
[9]   NF-kB in development and progression of human cancer [J].
Dolcet, X ;
Llobet, D ;
Pallares, J ;
Matias-Guiu, X .
VIRCHOWS ARCHIV, 2005, 446 (05) :475-482
[10]   CD95/Fas signaling in human melanoma cells: conditional expression of CD95L/FasL overcomes the intrinsic apoptosis resistance of malignant melanoma and inhibits growth and progression of human melanoma xenotransplants [J].
Eberle, J ;
Fecker, LF ;
Hossini, AM ;
Wieder, T ;
Daniel, PT ;
Orfanos, CE ;
Geilen, CC .
ONCOGENE, 2003, 22 (57) :9131-9141