CLINICAL TRIAL: A PHASE I STUDY IN ADVANCED SOLID MALIGNANCIES (NCI 7967)

临床试验：晚期实体恶性肿瘤的 I 期研究 (NCI 7967)

• 批准号: 7951279
• 负责人: CHANDRA BELANI
• 金额: $ 0.42万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951279
• 关键词: Carboplatin; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; DNA Damage; DNA Repair; Dose; Drug resistance; Enzymes; Funding; Genotoxic Stress; Grant; Institution; Link; Malignant Neoplasms; Normal Cell; Nuclear; PARP inhibition; Paclitaxel; Patients; Phase I Clinical Trials; Phase II Clinical Trials; Play; Poly Adenosine Diphosphate Ribose; Radiation therapy; Research; Research Personnel; Resources; Role; Solid; Source; United States National Institutes of Health; chemotherapy; inhibitor/antagonist; neoplastic cell; overexpression; small molecule; therapy design

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABT-888 is an orally available, small molecule inhibitor of poly(ADP-ribose) polymerease (PARP). PARP is an essential nuclear enzyme that plays a role in recognition of DNA damage and facilitation of DNA repair. Therefore, inhibition of PARP is expected to enhance the effects of DNA damage. Expression of PARP is higher in tumor cells as compared to normal cells. This overexpression has been linked to drug resistance and the ability of tumor cells to withstand genotoxic stress. It is anticipated that PARP inhibitors will function as sensitizing agents for chemotherapy and radiation therapy that are designed to cause DNA damage. The primary objective of the study is to determine the recommended dose for Phase 2 studies of ABT-888 that can be administered in combination with carboplatin and paclitaxel in patients who have advanced solid malignancies.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 ABT-888是一种口服的小分子抑制剂（ADP-核糖）聚合物（PARP）。 PARP是一种必不可少的核酶，在识别DNA损伤和促进DNA修复方面发挥作用。 因此，预计PARP的抑制会增强DNA损伤的影响。 与正常细胞相比，肿瘤细胞中PARP的表达更高。 这种过表达与耐药性和肿瘤细胞承受遗传毒性应激的能力有关。 预计PARP抑制剂将充当旨在引起DNA损伤的化学疗法和放射疗法的敏化剂。 该研究的主要目的是确定ABT-888的2阶段研究的建议剂量，这些剂量可以与患有固体恶性肿瘤的患者中与卡泊蛋白和紫杉醇结合使用。