UT-MD Anderson Cancer Centre, Department of Gastrointestinal Medical Oncology, 1515 Holcombe Boulevard, Unit 426, Houston, TX 77030, USA.
Br J Cancer. 2011 Oct 11;105(8):1114-22. doi: 10.1038/bjc.2011.382.
Historically, PARP inhibitors (PARPi) were developed to potentiate the cytotoxic effect of certain chemotherapeutic agents and are currently being investigated in combination with chemotherapy in diverse cancer types. These agents are also radiosensitisers and clinical trials of PARPi with concurrent radiation are required. It has long been recognised that defective DNA repair pathways lead to tumour susceptibility. Recent studies indicate that tumour cells with defective homologous recombination (HR) repair pathways, the classic example being BRCA mutations, are exquisitely sensitive to PARPi. Defects in HR are not restricted to BRCA-associated tumours and other cancer types may be enriched for HR defects and hence susceptible to PARP inhibition. The identification of predictive markers for sensitivity to PARP inhibition is a priority area for research.
从历史上看，PARP 抑制剂 (PARPi) 的开发是为了增强某些化疗药物的细胞毒性作用，目前正在多种癌症类型中与化疗联合进行研究。这些药物也具有放射增敏作用，需要进行 PARPi 与放射治疗同时进行的临床试验。长期以来，人们一直认识到，DNA 修复途径的缺陷会导致肿瘤易感性。最近的研究表明，具有缺陷同源重组 (HR) 修复途径的肿瘤细胞，典型的例子是 BRCA 突变，对 PARPi 非常敏感。HR 缺陷不仅限于 BRCA 相关肿瘤，其他癌症类型可能富集 HR 缺陷，因此容易受到 PARP 抑制的影响。鉴定对 PARP 抑制敏感的预测标志物是研究的优先领域。
