To: scaram(o)uche who wrote (44 ) 4/19/2001 3:06:02 PM From: keokalani'nui Read Replies (1) | Respond to Dr. Claudio Conti (MD Anderson Cancer Center; Houston, TX) presented results with transgenic animal models for the development of novel therapeutic strategies for cancer treatment. Dr. Conti gave an overview of classic animal models such as rodent carcinogenesis and immunocompromised mice. The former have been used to investigate chemical carcinogenesis, and more recently to design cancer prevention strategies. Xenotransplants in nude mice have been widely used as a strategy to understand the in vivo behavior of tumor cell lines, and assess chemosensitivity to different agents. The speaker acknowledged the deep changes in this field of research brought about by genetically modified animals. New technologies have allowed researchers to introduce oncogenes or delete tumor-suppressor genes in these animals. Moreover, normal mouse genes can be replaced with mutated genes such as those frequently found in human tumors. These new, genetically modified animal models are now playing a key role in the preclinical development of novel therapeutic strategies. Thousands of new genes have been recently cloned. Their biological function is not yet fully elucidated, however. Characterizing these genes will in part involve both in vivo and in vitro models. Genetically modified mice will probably clarify some of the metabolic pathways related to newly discovered therapeutic targets. Besides their contribution in dissecting target metabolic pathways, new animal models have allowed in vivo drug testing against these cellular functions in a setting genetically modified to reproduce molecular changes usually found in human cancers. Dr. Conti selected two specific examples: the use of transgenic and knockout animals (those carrying a specific deletion of a key gene) related to cell cycle control or angiogenesis. For example, animal models showed that the cyclin D1 and cdk4 genes could be deleted with minimal effects on normal cells, but with a profound impact on tumor cells. This differential effect makes these molecules ideal candidates for development of novel therapeutic strategies. Two additional mouse models related to angiogenesis were described, with either overexpression or ablation of the VEGF gene. Message 15679867
