Mulshine J L, Jett M, Cuttitta F, Treston A M, Quinn K, Scott F, Iwai N, Avis I, Linnoila R I, Shaw G L
Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850.
Cancer. 1993 Aug 1;72(3 Suppl):978-83. doi: 10.1002/1097-0142(19930801)72:3+<978::aid-cncr2820721305>3.0.co;2-t.
Promising cancer clinical trials results involving the disruption of early stages of cancer with intervention agents such as tamoxifen or retinoids have led to significant new research interest in developing preventative strategy for the control of epithelial cancers. Key to the efficient progress in this field is a clear understanding of the complex biology of the early stages of cancerization that proceed on the epithelial surface. Systematic analysis of the biology of strategic targets such as growth factors is one approach to this problem. Gastrin-releasing peptide is an autocrine growth factor for certain types of lung cancer cells. Mechanisms involved in the production and activation of this peptide are discussed as an example of how rational approaches to neutralization of cancer promotion biology can be achieved. The tools to monitor the success of this type of intervention also emerge from the understanding of the biology of growth factors, and intermediate end point markers that determine the presence or effects of a growth factor are attractive candidates for evaluation. Additional biologic tools reflecting the early stages of the cancer process need to be validated for use in serially evaluating the status of the relevant epithelium so that the ongoing success of a cancer intervention procedure can be established. Through this type of translational research, important applications of molecular biology may greatly improve the success of preventative strategies for cancer control.
涉及使用他莫昔芬或类视黄醇等干预剂破坏癌症早期阶段的有前景的癌症临床试验结果，引发了人们对制定控制上皮癌预防策略的重大新研究兴趣。该领域取得有效进展的关键在于清楚了解在上皮表面发生的癌化早期阶段的复杂生物学特性。对生长因子等战略靶点的生物学进行系统分析是解决这个问题的一种方法。胃泌素释放肽是某些类型肺癌细胞的自分泌生长因子。本文以该肽的产生和激活机制为例，探讨了如何实现中和癌症促进生物学的合理方法。监测这类干预成功与否的工具也来自对生长因子生物学的理解，而决定生长因子存在或作用的中间终点标志物是有吸引力的评估候选指标。还需要验证反映癌症进程早期阶段的其他生物学工具，以便用于连续评估相关上皮的状态，从而确定癌症干预程序的持续有效性。通过这类转化研究，分子生物学的重要应用可能会大大提高癌症控制预防策略的成功率。
