PARP抑制剂在卵巢癌治疗中的研究进展

Research Progress in Poly ADP-ribose Polymerase Inhibitors for Ovarian Cancer Treatment

卵巢癌起病隐匿,发现时多处于疾病晚期,目前在妇科恶性肿瘤的病死率中居首位,大多数患者死于肿瘤复发和耐药。聚二磷酸腺苷(ADP)核糖聚合酶(poly ADP-ribose polymerase,PARP)抑制剂是一种卵巢癌靶向治疗的新药,能选择性抑制PARP功能以达到靶向治疗的目的。大量试验显示,PARP抑制剂在具有乳腺癌易感基因(BRCA)突变的卵巢癌中有抗肿瘤作用,且有良好的耐受性。PARP抑制剂能显著延长携带BRCA基因突变的卵巢癌患者的疾病无进展生存时间,尤其对铂类敏感、携带BRCA基因突变的卵巢癌患者获益最大。综述PARP抑制剂的作用机制及其代表药物在卵巢癌治疗的临床研究进展。

Ovarian cancer is a malignant cancer with insidious onset, and it remains the leading cause of death from gynecological malignancies. Most ovarian cancer patients die of recurrences and drug-resistance. Poly ADP-ribose polymerase （PARP） inhibitors emerge as a new class of targeted agents for ovarian cancer. PARP inhibitors can inhibit PARP enzyme as target in BRCA mutation-positive cells. With a number of clinical trials have shown, PARP inhibitors have anti-cancer effect on ovarian cancer with BRCA mutations. And the adverse effects are well tolerated. As clinical trials shown, PARP inhibitors prolong significantly the progress free survival of ovarian cancer patients with BRCA deficiency. In addition, PARP inhibitors are most active in platinum-sensitive, BRCA mutation-positive ovarian cancer. This review discusses the mechanism of PARP inhibitors as well as the clinical development of this class of anti-cancer agents in ovarian cancer treatment.