Phase 01 Clinical Trials

01期临床试验

• 批准号: 8552970
• 负责人: James Doroshow
• 金额: $ 39.29万
• 依托单位: DIVISION OF BASIC 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/8552970
• 关键词: Antineoplastic Agents; Biological Assay; Biopsy; CCR; Clinical; Clinical Trials; Collaborations; DNA Double Strand Break; DNA Methyltransferase Inhibitor; Development; Goals; Human; Immunofluorescence Immunologic; Laboratories; Medical Oncology; Molecular; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Poly(ADP-ribose) Polymerases; System; Tetrahydrouridine; Therapeutic Agents; Topoisomerase-I Inhibitor; Tumor Tissue; Type I DNA Topoisomerases; United States National Institutes of Health; cancer diagnosis; cancer therapy; detector; inhibitor/antagonist; insight; novel; novel therapeutics

The collaboration between the LMP and DCTD has been responsible for the development of several new pharmacodynamic assays, including an ultrasensitive immunofluorescence assay for gamma H2AX (DNA double strand break detector) in tumor tissue biopsies, and ELISAs for topoisomerase I and poly ADP-ribose polymerase (PARP). These assays have been essential for first in human clinical trials of PARP inhibitors in combination with topoisomerase I inhibitors as well as of novel, non-camptothecin topoismerase I inhibitors that have been activated in the NIH Clinical Center. In addition, collaborations with the Medical Oncology Branch have facilitated the development of the new DNA methyltransferase inhibitor fluorodeoxycytidine used in combination with tetrahydrouridine, drugs that have been produced by DCTD for study by the CCR. Additional collaborations have developed around our use of the NCI 60 for systems pharmacology.

LMP和DCTD之间的合作负责开发几种新的药效学检测方法，包括肿瘤组织活检中γ H2 AX（DNA双链断裂检测器）的超灵敏免疫荧光检测，以及拓扑异构酶I和聚ADP-核糖聚合酶（PARP）的ELISA。这些测定对于PARP抑制剂与拓扑异构酶I抑制剂联合使用以及NIH临床中心已激活的新型非喜树碱拓扑异构酶I抑制剂的首次人体临床试验至关重要。此外，与医学肿瘤学分支的合作促进了与四氢尿苷联合使用的新型DNA甲基转移酶抑制剂氟脱氧胞苷的开发，DCTD已生产这些药物供CCR研究。 围绕我们使用NCI 60进行系统药理学研究，还开展了其他合作。