Christian M C, Pluda J M, Ho P T, Arbuck S G, Murgo A J, Sausville E A
Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA.
Semin Oncol. 1997 Apr;24(2):219-40.
The Division of Cancer Treatment, Diagnosis and Centers of the National Cancer Institute (NCI) has a large program in clinical cancer therapeutics development. It currently holds investigational new drug applications for nearly 200 agents with which it sponsors clinical trials. In addition, it has a major preclinical development program. With the tremendous advances in our understanding of molecular and tumor biology during the past decade, the NCI's portfolio of agents has expanded beyond classical cytotoxic agents to include a wide variety of new molecular and therapeutic targets. In addition to agents with more conventional mechanisms of action, the NCI has targeted therapeutics programs that focus on tumor vasculature, cell cycle control and cell signaling, mechanisms of apoptosis, invasion and metastasis, and immunological recognition and response. Each of these focused areas includes agents of different classes and modes of action that are all directed at the target of interest. The scope of the NCI's program allows it to respond to incorporate promising new agents or targets as they arise and to prioritize them for use of preclinical and clinical resources. Agents in development through the NCI are derived from a number of diverse sources including its own screening efforts, academia, and numerous collaborations with the pharmaceutical and biotechnology industries. NCI works closely with collaborators to ensure complementary, non-duplicative clinical development and attempts to ensure that the full potential of promising agents is explored. A number of compounds in early clinical development or about to enter the clinic are discussed briefly in this manuscript.
美国国立癌症研究所（NCI）的癌症治疗、诊断与中心部门在临床癌症治疗药物研发方面开展了大型项目。该部门目前持有近200种药物的研究性新药申请，并以此赞助临床试验。此外，它还有一个重要的临床前研发项目。在过去十年里，随着我们对分子生物学和肿瘤生物学的理解取得巨大进展，NCI的药物组合已从传统的细胞毒性药物扩展到包括多种新的分子和治疗靶点。除了具有更传统作用机制的药物外，NCI还有针对肿瘤血管生成、细胞周期调控和细胞信号传导、细胞凋亡机制、侵袭与转移以及免疫识别与反应的治疗项目。这些重点领域中的每一个都包括不同类别和作用方式的药物，它们都针对感兴趣的靶点。NCI项目的规模使其能够在有前景的新药物或靶点出现时做出回应，并对它们进行优先排序，以便利用临床前和临床资源。通过NCI进行研发的药物来源多样，包括其自身的筛选工作、学术界以及与制药和生物技术行业的众多合作。NCI与合作伙伴密切合作，以确保临床开发具有互补性且不重复，并试图确保探索有前景药物的全部潜力。本文简要讨论了一些处于临床早期开发阶段或即将进入临床的化合物。
