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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 ABT-888是一种口服的小分子聚腺苷二磷酸核糖聚合酶(PARP)抑制剂。PARP是一种重要的核酶，在识别DNA损伤和促进DNA修复方面发挥着重要作用。因此，抑制PARP有望增强DNA损伤的效果。PARP在肿瘤细胞中的表达高于正常细胞。这种过度表达与抗药性和肿瘤细胞承受基因毒性应激的能力有关。预计PARP抑制剂将作为化疗和放射治疗的增敏剂，旨在导致DNA损伤。 这项研究的主要目标是确定ABT-888第二阶段研究的推荐剂量，该药物可与卡铂和紫杉醇联合应用于晚期实体恶性肿瘤患者。

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.