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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 ABT-888是一种口服有效的聚（ADP-核糖）聚合酶（PARP）小分子抑制剂。 PARP是一种重要的核酶，在识别DNA损伤和促进DNA修复中发挥作用。 因此，PARP的抑制预期会增强DNA损伤的作用。 PARP在肿瘤细胞中的表达高于正常细胞。 这种过度表达与耐药性和肿瘤细胞耐受遗传毒性应激的能力有关。 预期PARP抑制剂将用作设计用于引起DNA损伤的化疗和放疗的敏化剂。 本研究的主要目的是确定ABT-888 2期研究的推荐剂量，该研究可与卡铂和紫杉醇联合治疗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.