Models for prevention and treatment of cancer: Problems vs promises

被引:122
作者
Aggarwal, Bharat B. [1 ]
Danda, Divya [1 ]
Gupta, Shan [1 ]
Gehlot, Prashasnika [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Cytokine Res Lab, Dept Expt Therapeut, Houston, TX 77030 USA
关键词
Cancer; Cell signaling; Pathogenesis; Therapeutic targets; GROWTH-FACTOR RECEPTOR; PHASE-III TRIAL; HUMAN TUMOR XENOGRAFTS; PRIMARY BREAST-CANCER; PERSONALIZED MEDICINE; STEM-CELLS; TRASTUZUMAB RESISTANCE; CROSS-CONTAMINATION; SIGNALING PATHWAYS; PLUS CAPECITABINE;
D O I
10.1016/j.bcp.2009.05.027
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Current estimates from the American Cancer Society and from the International Union Against Cancer indicate that 12 million cases of cancer were diagnosed last year, with 7 million deaths worldwide: these numbers are expected to double by 2030 (27 million cases with 17 million deaths). Despite tremendous technological developments in all areas, and President Richard Nixon's initiative in the 1974 "War against Cancer", the US cancer incidence is the highest in the world and the cancer death rate has not significantly changed in the last 50 years (193.9 per 100,000 in 1950 vs 193.4 per 100,000 in 2002). Extensive research during the same time, however, has revealed that cancer is a preventable disease that requires major changes in life style; with one third of all cancers assigned to Tobacco, one third to diet, and remaining one third to the environment. Approximately 20 billion dollars are spent annually to find a cure for cancer. We propose that our inability to find a cure to cancer lies in the models used. Whether cell culture or animal studies, no model has yet been found that can reproduce the pathogenesis of the disease in the laboratory. Mono-targeted therapies, till know in most cases, have done a little to make a difference in cancer treatment. Similarly, molecular signatures/predictors of the diagnosis of the disease and response are also lacking. This review discusses the pros and cons of current cancer models based on cancer genetics, cell culture, animal models, cancer biomarkers/signature, cancer stem cells, cancer cell signaling, targeted therapies, therapeutic targets, clinical trials, cancer prevention, personalized medicine, and off-label uses to find a cure for cancer and demonstrates an urgent need for "out of the box" approaches. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:1083 / 1094
页数:12
相关论文
共 125 条
[31]   Clonogenic assay with established human tumour xenografts:: correlation of in vitro to in vivo activity as a basis for anticancer drug discovery [J].
Fiebig, HH ;
Maier, A ;
Burger, AM .
EUROPEAN JOURNAL OF CANCER, 2004, 40 (06) :802-820
[32]   Sorafenib in renal cell carcinoma [J].
Flaherty, Keith T. .
CLINICAL CANCER RESEARCH, 2007, 13 (02) :747S-752S
[33]   The Role of Parental and Grandparental Epigenetic Alterations in Familial Cancer Risk [J].
Fleming, Jessica L. ;
Huang, Tim H-M. ;
Toland, Amanda Ewart .
CANCER RESEARCH, 2008, 68 (22) :9116-9121
[34]   A census of human cancer genes [J].
Futreal, PA ;
Coin, L ;
Marshall, M ;
Down, T ;
Hubbard, T ;
Wooster, R ;
Rahman, N ;
Stratton, MR .
NATURE REVIEWS CANCER, 2004, 4 (03) :177-183
[35]  
Gant TW, 2009, CURR OPIN DRUG DISC, V12, P72
[36]  
Garodia Prachi, 2007, J Soc Integr Oncol, V5, P25, DOI 10.2310/7200.2006.029
[37]   Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2 [J].
Gennari, R ;
Menard, S ;
Fagnoni, F ;
Ponchio, L ;
Scelsi, M ;
Tagliabue, E ;
Castiglioni, F ;
Villani, L ;
Magalotti, C ;
Gibelli, N ;
Oliviero, B ;
Ballardini, B ;
Da Prada, G ;
Zambelli, A ;
Costa, A .
CLINICAL CANCER RESEARCH, 2004, 10 (17) :5650-5655
[38]   Introduction to 'A multitargeted approach: clinical advances in the treatment of solid tumours' [J].
George, D. ;
Verweij, J. .
ANNALS OF ONCOLOGY, 2007, 18 :1-2
[39]   Lapatinib plus capecitabine for HER2-positive advanced breast cancer [J].
Geyer, Charles E. ;
Forster, John ;
Lindquist, Deborah ;
Chan, Stephen ;
Romieu, C. Gilles ;
Pienkowski, Tadeusz ;
Jagiello-Gruszfeld, Agnieszka ;
Crown, John ;
Chan, Arlene ;
Kaufman, Bella ;
Skarlos, Dimosthenis ;
Campone, Mario ;
Davidson, Neville ;
Berger, Mark ;
Oliva, Cristina ;
Rubin, Stephen D. ;
Stein, Steven ;
Cameron, David .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (26) :2733-2743
[40]  
GIOVANELLA BC, 1972, JNCI-J NATL CANCER I, V48, P1531