Multitarget drugs: the present and the future of cancer therapy

被引:0
作者
Petrelli, Annalisa [1 ]
Valabrega, Giorgio [1 ]
机构
[1] Univ Turin, Sch Med, Inst Canc Res & Treatment IRCC, Div Mol Oncol, I-10060 Turin, Italy
关键词
cancer therapy; clinical trials; multitarget; oncogene addiction; stroma; tyrosine kinase inhibitors; GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; BREAST-CARCINOMA CELLS; ENDOTHELIAL-CELLS; PHASE-II; ANTISENSE OLIGONUCLEOTIDES; ANTITUMOR-ACTIVITY; MAMMARY-CARCINOMA; TUMOR PROGRESSION; SURROGATE MARKER;
D O I
10.1517/14656560902781907
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Target therapies for the treatment of human cancers have revolutionized the concept of oncological medicine. This type of therapeutic approach is directed to the inhibition of molecular targets that play a pivotal role in tumor progression - such as tyrosine kinase receptors (TKIs) controlling cell proliferation and survival - mainly by means of compounds able to block their activity. In the beginning, the aim of target therapies was specifically to hit a single molecule expressed in neoplastic cells. Now the prevailing idea is that inhibiting both cancer cells and cells of the stroma supporting the tumor would gain better results in fighting the disease. Therefore, the single-target therapy is fading in favor of a multitarget approach and the new generation of TKIs is selected on the basis of their ability simultaneously to target different molecules. This review summarizes the molecular basis of multitarget therapies and the most relevant results obtained in different cancer types.
引用
收藏
页码:589 / 600
页数:12
相关论文
共 92 条
[21]   Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors [J].
Demetri, GD ;
von Mehren, M ;
Blanke, CD ;
Van den Abbeele, AD ;
Eisenberg, B ;
Roberts, PJ ;
Heinrich, MC ;
Tuveson, DA ;
Singer, S ;
Janicek, M ;
Fletcher, JA ;
Silverman, SG ;
Silberman, SL ;
Capdeville, R ;
Kiese, B ;
Peng, B ;
Dimitrijevic, S ;
Druker, BJ ;
Corless, C ;
Fletcher, CDM ;
Joensuu, H .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (07) :472-480
[22]   Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial [J].
Demetri, George D. ;
van Oosterom, Allan T. ;
Garrett, Christopher R. ;
Blackstein, Martin E. ;
Shah, Manisha H. ;
Verweij, Jaap ;
McArthur, Grant ;
Judson, Ian R. ;
Heinrich, Michael C. ;
Morgan, Jeffrey A. ;
Desai, Jayesh ;
D Fletcher, Christopher ;
George, Suzanne ;
Bello, Carlo L. ;
Huang, Xin ;
Baum, Charles M. ;
Casali, Paolo G. .
LANCET, 2006, 368 (9544) :1329-1338
[23]   Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification [J].
DePrimo, SE ;
Wong, LM ;
Khatry, DB ;
Nicholas, SL ;
Manning, WC ;
Smolich, BD ;
O'Farrell, AM ;
Cherrington, JM .
BMC CANCER, 2003, 3 (1)
[24]   MUTATIONS IN THE RET PROTOONCOGENE ARE ASSOCIATED WITH MEN 2A AND FMTC [J].
DONISKELLER, H ;
DOU, SS ;
CHI, D ;
CARLSON, KM ;
TOSHIMA, K ;
LAIRMORE, TC ;
HOWE, JR ;
MOLEY, JF ;
GOODFELLOW, P ;
WELLS, SA .
HUMAN MOLECULAR GENETICS, 1993, 2 (07) :851-856
[25]  
DUTCHER JP, 2008, J CLIN ONCOL 0520, V26
[26]   Sorafenib in advanced clear-cell renal-cell carcinoma [J].
Escudier, Bernard ;
Eisen, Tim ;
Stadler, Walter M. ;
Szczylik, Cezary ;
Oudard, Stephane ;
Siebels, Michael ;
Negrier, Sylvie ;
Chevreau, Christine ;
Solska, Ewa ;
Desai, Apurva A. ;
Rolland, Frederic ;
Demkow, Tomasz ;
Hutson, Thomas E. ;
Gore, Martin ;
Freeman, Scott ;
Schwartz, Brian ;
Shan, Minghua ;
Simantov, Ronit ;
Bukowski, Ronald M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :125-134
[27]   Molecular basis for sunitinib efficacy and future clinical development [J].
Faivre, Sandrine ;
Demetri, George ;
Sargent, William ;
Raymond, Eric .
NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (09) :734-745
[28]   Reversible tumorigenesis by MYC in hematopoietic lineages [J].
Felsher, DW ;
Bishop, JM .
MOLECULAR CELL, 1999, 4 (02) :199-207
[29]  
FIGLIN A, 2008, J CLIN ONCOL S, V26
[30]  
FRIEDLANDER M, 2007, J CLIN ONCOL S, V25, P18