Yeatman Timothy J, Chambers Ann F
H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
Clin Exp Metastasis. 2003;20(1):85-90. doi: 10.1023/a:1022502805474.
Human colon cancer affects nearly 150,000 patients and results in 60,000 deaths in the United States per year. Despite significant advances in the management of the colon cancer patient, little change in survival rates has been appreciated over the past 50 years. The primary cause of death relates to the development of distant metastases to organs such as the liver and lungs. Colon cancer represents an important disease to study in order to better understand tumor progression and metastasis primarily because there is almost a stepwise advancement of the disease that is marked by measurable genetic and associated phenotypic alterations. Metastasis appears to be the end product of the development of 'Herculean' cell clones capable of independent growth, invasion, adhesion, avoidance of apoptosis, and angiogenesis. Although significant progress has been made in understanding the sequential genetic events leading to the development of cancer, the precise genes and the associated molecular pathways underlying the development of metastatic potential are still poorly understood. Moreover, our enhanced genetic knowledge has had relatively little trickle down effect on our clinical management of this deadly disease. For this reason, we undertook a comprehensive study to develop a molecular encyclopedia of new tumor markers and markers of tumor progression, some of which will hopefully prove useful in the clinical management of colon cancer patients by means of their capacity to detect and predict the stage and disease burden. This review will focus on the application of gene expression profiling technology to the problem of identifying new tumor markers and progression markers, and the discovery of osteopontin as the leading candidate clinical marker derived from a screen of approximately 12,000 named genes.
在美国,每年有近15万名患者受到人类结肠癌的影响,导致6万人死亡。尽管在结肠癌患者的治疗方面取得了重大进展,但在过去50年里,生存率几乎没有变化。主要死亡原因与癌细胞转移至肝脏和肺等远处器官有关。结肠癌是一种重要的研究疾病,以便更好地了解肿瘤进展和转移,主要是因为该疾病几乎呈现出一种逐步发展的过程,其特征是可测量的基因和相关表型改变。转移似乎是能够独立生长、侵袭、黏附、逃避凋亡和血管生成的“强大”细胞克隆发展的最终产物。尽管在理解导致癌症发生的一系列遗传事件方面取得了重大进展,但对于转移潜能发展背后的确切基因和相关分子途径仍知之甚少。此外,我们日益增长的遗传学知识对这种致命疾病的临床治疗产生的影响相对较小。因此,我们开展了一项全面研究,以编制一份新的肿瘤标志物和肿瘤进展标志物的分子百科全书,其中一些有望通过其检测和预测疾病分期及负担的能力,在结肠癌患者的临床治疗中发挥作用。本综述将重点关注基因表达谱技术在识别新的肿瘤标志物和进展标志物问题上的应用,以及从大约12000个命名基因的筛选中发现骨桥蛋白作为主要候选临床标志物的情况。