The CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
Breast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, UK.
Open Biol. 2022 Jul;12(7):220118. doi: 10.1098/rsob.220118. Epub 2022 Jul 27.
PARP inhibitors (PARPi) have been demonstrated to exhibit profound anti-tumour activity in individuals whose cancers have a defect in the homologous recombination DNA repair pathway. Here, we describe the current consensus as to how PARPi work and how drug resistance to these agents emerges. We discuss the need to refine the current repertoire of clinical-grade companion biomarkers to be used with PARPi, so that patient stratification can be improved, the early emergence of drug resistance can be detected and dose-limiting toxicity can be predicted. We also highlight current thoughts about how PARPi resistance might be treated.
多聚二磷酸腺苷核糖聚合酶抑制剂（PARPi）已被证实对同源重组 DNA 修复途径缺陷的癌症患者具有显著的抗肿瘤活性。在此，我们描述了 PARPi 作用机制以及这些药物产生耐药性的方式的现有共识。我们讨论了需要改进目前临床级伴随生物标志物的应用范围，以与 PARPi 一起使用，从而改善患者分层、早期检测药物耐药性并预测剂量限制毒性。我们还强调了目前关于如何治疗 PARPi 耐药性的一些想法。
