The use of xenograft models for the selection of cancer treatments with the EGFR as an example.
Mouse models of cancer have consistently been used to qualify new anti-cancer drugs for development of human clinical trials. The most used models are xenografts of human tumors grown subcutaneously in immunodeficient mice such as athymic (nude) or severe combined immune deficient (SCID) mice. However, the number of anti-cancer agents that fail in the clinic far outweighs those considered effective, suggesting that the selection procedure for progression of molecules into the clinic requires improvement. This has provoked considerable skepticism about the value of using such preclinical models. As a result, a shift has occurred towards developing and using spontaneous mouse tumor arising in transgenic and/or knockout mice engineered to recapitulate various genetic alterations thought to be causative of specific types of human cancers. Alternatively, the option has been to improve human tumor xenograft models by using orthotopic transplantation and, therefore, promotion of metastatic spread of the resultant 'primary' tumors. Here we review the value and the limitations of xenograft models and their role in developing new anti-cancer treatments.
Troiani
Teresa
T
Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F Magrassi e A Lanzara, Seconda Università degli Studi di Napoli, Naples, Italy.
Schettino
Clorinda
C
Martinelli
Erika
E
Morgillo
Floriana
F
Tortora
Giampaolo
G
Ciardiello
Fortunato
F
D000818:Animals; D000970:Antineoplastic Agents; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D066246:ErbB Receptors