Khaddour Karam, Felipe Fernandez Manuel, Khabibov Marsel, Garifullin Airat, Dressler Danielle, Topchu Iuliia, Patel Jyoti D, Weinberg Frank, Boumber Yanis
Division of Hematology and Oncology, Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cancers (Basel). 2022 Oct 28;14(21):5305. doi: 10.3390/cancers14215305.
Lung cancer remains the second most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. The mapping of genomic alterations and their role in lung-cancer progression has been followed by the development of new therapeutic options. Several novel drugs, such as targeted therapy and immunotherapy, have significantly improved outcomes. However, many patients with lung cancer do not benefit from existing therapies or develop progressive disease, leading to increased morbidity and mortality despite initial responses to treatment. Alterations in DNA-damage repair (DDR) genes represent a cancer hallmark that impairs a cell's ability to prevent deleterious mutation accumulation and repair. These alterations have recently emerged as a therapeutic target in breast, ovarian, prostate, and pancreatic cancers. The role of DDR alterations remains largely unknown in lung cancer. Nevertheless, recent research efforts have highlighted a potential role of some DDR alterations as predictive biomarkers of response to treatment. Despite the failure of PARP inhibitors (main class of DDR targeting agents) to improve outcomes in lung cancer patients, there is some evidence suggesting a role of PARP inhibitors and other DDR targeting agents in benefiting a distinct subset of lung cancer patients. In this review, we will discuss the existing literature on DDR alterations and homologous recombination deficiency (HRD) state as predictive biomarkers and therapeutic targets in both non-small cell lung and small cell lung cancer.
肺癌仍然是全球第二大常见诊断癌症，也是癌症相关死亡的主要原因。随着基因组改变的图谱绘制及其在肺癌进展中的作用的研究，新的治疗选择得以开发。几种新型药物，如靶向治疗和免疫治疗，显著改善了治疗结果。然而，许多肺癌患者无法从现有治疗中获益或出现疾病进展，尽管最初对治疗有反应，但仍导致发病率和死亡率上升。DNA损伤修复（DDR）基因的改变是一种癌症标志，它损害了细胞预防有害突变积累和修复的能力。这些改变最近已成为乳腺癌、卵巢癌、前列腺癌和胰腺癌的治疗靶点。DDR改变在肺癌中的作用在很大程度上仍然未知。然而，最近的研究工作强调了一些DDR改变作为治疗反应预测生物标志物的潜在作用。尽管聚腺苷二磷酸核糖聚合酶（PARP）抑制剂（DDR靶向药物的主要类别）未能改善肺癌患者的治疗结果，但有一些证据表明PARP抑制剂和其他DDR靶向药物对一部分特定的肺癌患者有益。在这篇综述中，我们将讨论关于DDR改变和同源重组缺陷（HRD）状态作为非小细胞肺癌和小细胞肺癌的预测生物标志物及治疗靶点的现有文献。
