Generation of drug-resistant tumors using intermittent dosing of tyrosine kinase inhibitors in mouse.
Generation of drug-resistant tumors using intermittent dosing of tyrosine kinase inhibitors in mouse.
复制标题
使用间歇性给药小鼠酪氨酸激酶抑制剂产生耐药肿瘤。
DOI：
10.1101/pdb.prot077842
复制
发表时间：
2014
影响因子：
--
通讯作者：
Politi,Katerina
中科院分区：
文献类型：
--
作者：
Pirazzoli,Valentina;Politi,Katerina
对靶向治疗的耐药性已成为临床成功使用药物的主要障碍。因此，了解耐药的潜在分子机制是至关重要的战略，以确定预防和克服it.given的定义性质的致癌病变存在于基因工程小鼠模型（GEMMs）和相对容易的样品收集和分析，他们是理想的系统，其中概括的反应和随后出现的耐药性靶向治疗。当在GEMM中使用非常有效的根除肿瘤的药物时，获得耐药肿瘤可能是一个挑战。产生这种肿瘤的一种方法是使用次优间歇给药策略来治疗动物，这允许在没有药物的情况下肿瘤生长和进展的时期。这种间歇给药策略已成功用于研究肺癌模型对酪氨酸激酶厄洛替尼的耐药性，并在此处进行了描述。虽然该方案是特定于该实验系统的，但是概念和一般设计可以适于与其他癌症的GEMM一起使用。
Resistance to targeted therapies has emerged as a major hurdle for the successful use of drugs in the clinic. Therefore, understanding the underlying molecular mechanisms of drug resistance is crucial for the identification of strategies to prevent and overcome it. Given the defined nature of the oncogenic lesions present in genetically engineered mouse models (GEMMs) and the relative ease of sample collection and analysis, they are ideal systems in which to recapitulate the response and subsequent emergence of resistance to targeted therapies. When agents that are very effective at eradicating tumors are used in GEMMs, obtaining drug-resistant tumors can be a challenge. One approach to generating such tumors is the use of a suboptimal intermittent dosing strategy to treat the animals, which allows for periods of tumor growth and progression in the absence of drug. This intermittent dosing strategy has been used successfully to study resistance to the tyrosine kinase erlotinib in lung cancer models and is described here. Although this protocol is specific for this experimental system, the concepts and general design can be adapted for use with GEMMs of other cancers.