Department of Medical Oncology, University College London Hospital, London, UK.
Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
J Gynecol Oncol. 2022 May;33(3):e44. doi: 10.3802/jgo.2022.33.e44. Epub 2022 Mar 8.
The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.
聚腺苷二磷酸核糖聚合酶抑制剂（PARPi）在卵巢上皮癌患者中的应用正在扩大，从复发性疾病的应用扩展到一线治疗。这伴随着越来越多的患者出现获得性 PARPi 耐药。再加上那些对 PARPi 原发性耐药的患者，我们迫切需要更好地了解耐药机制，并寻找克服这种耐药性的方法。联合治疗通过与 PARPi 协同作用或通过恢复同源重组缺陷，通过另一种策略靶向同源重组修复途径，为克服内在和获得性耐药提供了潜力。我们讨论了 PARPi 耐药的机制和可能恢复 PARPi 敏感性的新型联合用药的数据。
