Washington University in St Louis, Campus Box 8064, 4th floor maternity, 4911 Barnes Jewish Hospital Plaza, St Louis, MO 63110, USA.
Expert Opin Investig Drugs. 2013 Mar;22(3):399-405. doi: 10.1517/13543784.2013.772135.
Patients with metastatic ovarian cancer continue to experience high recurrence rates and significant morbidity from standard treatments. There is a great need for efficacious tumor-specific agents in ovarian cancer. Iniparib (BSI-201) is a targeted drug currently under investigation.
The authors identified the mechanistic and clinical data available on the role of iniparib in ovarian cancer. Iniparib was initially thought to act via the poly-ADP ribose polymerase 1 (PARP-1) pathway, but recent studies have shown only nonspecific interactions between the drug and PARP proteins. Although iniparib is only active in cancer cells, the exact mechanism of action remains unclear. Iniparib was well tolerated at all dose levels in Phase I studies of solid organ malignancies. Preliminary data from Phase II studies of iniparib for the treatment of platinum-sensitive and platinum-resistant recurrent ovarian cancer show improvement in survival compared to historic controls. There are currently no Phase III studies.
Iniparib shows promise in early clinical trials; however, understanding the pathways of cytotoxicity will be crucial as cancer therapy becomes increasingly individualized.
转移性卵巢癌患者继续经历高复发率和标准治疗带来的显著发病率。卵巢癌非常需要有效的肿瘤特异性药物。尼拉帕尼（BSI-201）是一种目前正在研究的靶向药物。
作者确定了关于尼拉帕尼在卵巢癌中的作用的机制和临床数据。尼拉帕尼最初被认为通过聚 ADP 核糖聚合酶 1（PARP-1）途径发挥作用，但最近的研究表明，药物与 PARP 蛋白之间只有非特异性相互作用。尽管尼拉帕尼仅在癌细胞中活跃，但确切的作用机制仍不清楚。在实体恶性肿瘤的 I 期研究中，尼拉帕尼在所有剂量水平下均耐受良好。尼拉帕尼治疗铂敏感和铂耐药复发性卵巢癌的 II 期研究的初步数据显示，与历史对照相比，生存得到改善。目前尚无 III 期研究。
尼拉帕尼在早期临床试验中显示出希望；然而，随着癌症治疗变得越来越个体化，了解细胞毒性途径将至关重要。
