Clinical Development of Novel Drugs for Children with Refractory Cancers

儿童难治性癌症新药的临床开发

• 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
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7735408
• 关键词: Adult; BAY 54-9085; Carboxypeptidase G2; Child; Clinical; Clinical Research; Clinical Trials; Cytotoxic agent; Development; Drug Delivery Systems; Drug Kinetics; Drug effect disorder; End Point; Epothilone B Analogue; Human; Ixabepilone; Life; Malignant Childhood Neoplasm; Malignant Neoplasms; Methotrexate; Molecular; Neurofibromatosis 1; New Agents; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Population; Refractory; Solid Neoplasm; Therapeutic; Tubulin; Tyrosine Kinase Inhibitor; United States Food and Drug Administration; base; depolymerization; design; drug development; human FRAP1 protein; leukemia; mTOR Inhibitor; member; novel; programs; raf Kinases; receptor; tumor; young adult

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）部门的成员，我 参与开发儿童癌症的新药物，特别是 新的分子靶向药物。该项目的主要目标是开发新的 治疗儿童癌症的药物，强调更合理，更有针对性 基于目前对分子发病机制的理解的药物开发方法 人类的癌症。正在进行临床开发的新型分子靶向药物， 成人癌症将应用于儿童癌症的基础上的作用机制， 药物和儿童癌症靶点的重要性。raf激酶的研究进展 和受体酪氨酸激酶抑制剂索拉非尼为儿童难治性癌症服务 作为一个例子。mTOR通路参与人类癌症的进展， 神经纤维瘤病1型（NF 1）相关肿瘤，mTOR抑制剂的临床试验将 对两个患者群体都有好处。此外，新的临床开发 用于儿童癌症的细胞毒性剂，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剂，也将被 追求。将对这些药物的药代动力学和药效学进行研究和比较 在成人中的结果。甲氨蝶呤（MTX）解救剂的研究进展 羧肽酶-G2（CPDG 2）将继续使用，直到FDA批准这一潜在的 已经实现了挽救生命的治疗。

项目成果

Merlin PAKs a punch.

梅林重拳出击。

• DOI: 10.1097/00130404-200401000-00002
• 发表时间: 2004
• 期刊: Cancer journal (Sudbury, Mass.)
• 作者: Widemann,BrigitteC