Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, TO, Italy.
Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, TO, Italy.
Cancer Treat Rev. 2021 Sep;99:102256. doi: 10.1016/j.ctrv.2021.102256. Epub 2021 Jul 7.
The evaluation of the homologous recombination repair (HRR) status is emerging as a predictive tumor agnostic biomarker for poly (ADP-ribose) polymerase (PARP) inhibition across different tumor types and testing for HRR-signature is currently a developing area with promising therapeutic implications. Treatment with PARP inhibitors (PARPi) either as single agent or in combination with chemotherapy have shown so far limited activity in patients with thoracic malignancies. A deeper understanding of the biological background underlying HRR-deficient tumors, along with the recent advent of new effective targeted and immunotherapeutic agents, prompted the design of a new generation of clinical trials investigating novel PARPi-combinations in patients with lung cancer as well as malignant pleural mesothelioma. In this review we briefly summarize the biological basis of the DNA damage response pathway inhibition and provide an updated and detailed overview of clinical trials testing different PARPi-combinations strategies in patients with thoracic malignancies.
同源重组修复 (HRR) 状态的评估正在成为一种预测性的肿瘤不可知生物标志物，可用于不同肿瘤类型的聚（ADP-核糖）聚合酶 (PARP) 抑制，目前正在对 HRR 特征进行检测，这是一个具有广阔治疗前景的发展领域。PARP 抑制剂 (PARPi) 无论是单独使用还是与化疗联合使用，在胸部恶性肿瘤患者中的疗效都很有限。对 HRR 缺陷型肿瘤的生物学背景有了更深入的了解，再加上最近出现的新型有效靶向和免疫治疗药物，促使设计了新一代临床试验，研究新型 PARPi 联合治疗肺癌和恶性胸膜间皮瘤患者的疗效。在这篇综述中，我们简要总结了 DNA 损伤反应途径抑制的生物学基础，并对不同 PARPi 联合治疗策略在胸部恶性肿瘤患者中的临床试验进行了更新和详细的概述。
