Clinical Development of Novel Drugs for Children with Refractory Cancers

儿童难治性癌症新药的临床开发

基本信息

批准号：
7735408
负责人：
Brigitte Widemann
金额：
$ 14.24万
依托单位：
DIVISION OF CLINICAL SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

As a member of the Pharmacology and Experimental Therapeutics (PET) Section I am involved in the development of new agents for childhood cancers, particularly the application of new molecularly targeted drugs. The primary objective of this project is to develop new agents for the treatment of childhood cancers with an emphasis on a more rational, targeted approach of drug development based on the current understanding of the molecular pathogenesis of human cancers. New molecularly targeted agents that are undergoing clinical development for adult cancers will be applied to childhood cancers based on the mechanism of action of the drug and the importance of the target in childhood cancers. The development of the raf kinase and receptor tyrosine kinase inhibitor sorafenib for children with refractory cancers serves as an example. The mTOR pathway is involved in the progression of human cancers and neurofibromatosis type 1 (NF1) related tumors, and clinical trials with mTOR inhibitors will be pursued for both patient populations. In addition, the clinical development of novel cytotoxic agents for childhood cancers, such as the epothilone B analog ixabepilone (BMS-247550), an antitubulin agent, which inhibits tubulin depolymerization, will also be pursued. The pharmacokinetics and pharmacodynamics of these drugs will be studied and compared to results in adults. The development of the methotrexate (MTX) rescue agent carboxypeptidase-G2 (CPDG2) will be continued until FDA approval for this potentially life-saving treatment has been achieved.

作为药理学和实验治疗学 (PET) 组的成员，我参与儿童癌症新药物的开发，特别是新分子靶向药物的应用。该项目的主要目标是开发治疗儿童癌症的新药，重点是基于目前对人类癌症分子发病机制的了解，采用更合理、更有针对性的药物开发方法。基于药物的作用机制和靶点在儿童癌症中的重要性，正在针对成人癌症进行临床开发的新型分子靶向药物将应用于儿童癌症。用于治疗儿童难治性癌症的 raf 激酶和受体酪氨酸激酶抑制剂索拉非尼的开发就是一个例子。 mTOR 通路参与人类癌症和 1 型神经纤维瘤病 (NF1) 相关肿瘤的进展，并将针对这两种患者群体开展 mTOR 抑制剂的临床试验。此外，还将致力于针对儿童癌症的新型细胞毒性药物的临床开发，例如埃博霉素B类似物伊沙匹隆（BMS-247550），一种抑制微管蛋白解聚的抗微管蛋白药物。将研究这些药物的药代动力学和药效学，并与成人的结果进行比较。甲氨蝶呤 (MTX) 救援剂羧肽酶-G2 (CPDG2) 的开发将继续进行，直到 FDA 批准这种可能挽救生命的治疗方法。