NATURAL INHIBITORS OF CARCINOGENESIS

化学预防是一种治疗方法，通过口服能够抑制致癌过程的无毒药物来预防或推迟人类癌症的发生。作为国家抗击癌症努力的一个组成部分，这种方法的优点直观地说是显而易见的。已知多种潜在的癌症化学预防药物，其中大多数是在经验基础上发现的。我们已经组建了一个多学科团队，专注于发现和表征新的癌症化学预防药物，这些药物是天然产品或天然产品的衍生品。正如大量的先例所确立的那样，陆地植物提供了广泛的化学多样性。除了天然产物药物发现的实验过程外，一些对治疗人类疾病有用的独特成分是无法预料的。首先，从具有良好特征的饮食和非饮食植物体外生物测试小组开始，这些测试表明可以抑制癌症发生的主要阶段。活性物质在生理复杂性更高的二级检测系统中进行评估，那些具有这些二级鉴别器的活性物质受到生物测定指导的分级。活性成分在结构上由物理和光谱方法定义，在更广泛的生物测定系统中进行评估，并被认为是开发的候选药物。作为该计划项目的一部分，开发涉及化学合成或大规模分离，评估机制和结构-活性关系，并建立从现场到结构和机械定义的具有已证明治疗效果的化学实体的短期或长期癌症化学预防潜力。这些工作需要五个独立项目的努力，这五个项目得到两个核心组成部分和一个外部咨询委员会的协助。为了促进利用新发现的药物预防人类癌症，这是该计划项目的长期目标，与孟山都生命科学公司建立了正式的合作伙伴关系。该计划项目的所有要素都已被证明是有效的，我们预计未来将取得有增无减的进展。

Chemoprevention is a therapeutic method wherein human cancer is prevented or delayed through oral consumption of non-toxic agents capable of inhibiting the process of carcinogenesis. As an integral component of the national effort to defeat cancer, the merit of this approach is intuitively obvious. A variety of potential cancer chemopreventive agents are known, most of which were discovered on an empirical basis. We have assembled a multi-disciplinary team focused on the discovery and characterization of new cancer chemopreventive agents that are natural products or natural product derivatives. As established by ample precedent, terrestrial plants provide broad chemical diversity. Some unique constituents, useful for the treatment of human ailments, cannot be anticipated aside from the experimental process of natural product drug discovery. Starting with well-characterized dietary and non- dietary plant panel of in vitro bioassays indicative of inhibiting major stages of carcinogenesis. Active materials are evaluated in secondary assay systems of greater physiologic complexity, and those active with these secondary discriminators are subjected to bioassay-guided fractionation. Active principles are structurally-defined by physical and spectroscopic methods, evaluated in a broader array of bioassay systems, and considered as candidates for development. As part of this program project, development involves chemical synthesis or large-scale isolation, evaluation of mechanism and structure-activity relationships, and establishment of cancer chemopreventive potential in short- or long-term from the level of the field to the level of structurally- and mechanistically- defined chemical entities of proven therapeutic efficacy. These undertakings require the efforts of five separate projects that are assisted by two core components, and an External Advisory Board. To facilitate utilization of the newly discovered agents for the prevention of human cancers, the long-term objective of this program project, a formal partnership has been instituted with Monsanto Life Sciences. All elements of the program project have proven effective, and we anticipate unabated progress in the future.