Ghadimi B Michael, Grade Marian
Institute for Immunology, Technical University Dresden, Dresden, Germany.
Methods Mol Biol. 2010;576:327-39. doi: 10.1007/978-1-59745-545-9_16.
Preoperative treatment strategies are now recommended for a variety of human cancers. Unfortunately, the response of individual tumors to a preoperative treatment is not uniform, and ranges from complete regression to resistance. This poses a considerable clinical dilemma, because patients with a priori resistant tumors could either be spared exposure to radiation or DNA-damaging drugs, i.e., they could be referred to primary surgery or dose-intensified protocols could be pursued. Because the response of an individual tumor as well as therapy-induced side effects represent the major limiting factors of current treatment strategies, identifying molecular markers of response or for treatment toxicity have become exceedingly important. However, complex phenotypes such as tumor responsiveness to multimodal treatments probably do not depend on the expression levels of just one or a few genes and proteins. Therefore, methods that allow comprehensive interrogation of genetic pathways and networks hold great promise in delivering such tumor-specific signatures, because expression levels of tens of thousands of genes can be monitored simultaneously. During the past few years, microarray technology has emerged as a central tool in addressing pertinent clinical questions, the answers to which are critical for the realization of a personalized genomic medicine, in which patients will be treated based on the biology of their tumor and their genetic profile (1-4).
目前，多种人类癌症都推荐采用术前治疗策略。不幸的是，个体肿瘤对术前治疗的反应并不一致，从完全消退到耐药不等。这带来了相当大的临床困境，因为对术前治疗先验耐药的患者既可以避免接受放疗或DNA损伤药物治疗，也就是说，可以直接进行初次手术，或者采用剂量强化方案。由于个体肿瘤的反应以及治疗引起的副作用是当前治疗策略的主要限制因素，因此识别反应或治疗毒性的分子标志物变得极为重要。然而，诸如肿瘤对多模式治疗的反应性等复杂表型可能并不只取决于一个或几个基因和蛋白质的表达水平。因此，能够全面探究遗传途径和网络的方法在提供此类肿瘤特异性特征方面具有很大潜力，因为可以同时监测数万个基因的表达水平。在过去几年中，微阵列技术已成为解决相关临床问题的核心工具，这些问题的答案对于实现个性化基因组医学至关重要，在个性化基因组医学中，将根据患者肿瘤的生物学特性及其基因概况进行治疗（1-4）。
