Abstract：
BACKGROUND: Colorectal carcinoma (CRC) is one of the most common malignancies in the Western world, and metastatic disease is associated with a dismal prognosis. Poly-ADpribose polymerase (PARP) inhibitors gain increasing attention in the field of medical oncology, as they lead to synthetic lethality in malignancies with preexisting alterations in the DNA damage repair (DDR) pathway. As those alterations are frequently seen in CRC, a targeted approach through PARP inhibitors is expected to benefit these patients, both alone and in combination with other agents like chemotherapy, immunotherapy, antiangiogenics, and radiation.
OBJECTIVE: This review article aims to better clarify the role of PARP inhibitors as a treatment option in patients with metastatic CRC with alterations in the DDR pathway.
METHODS: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of PARP inhibitors in patients with metastatic CRC with homologous repair deficiency (HRD) and the correct line of therapy.
RESULTS: Current evidence supports the utilization of PARP inhibitors in CRC subgroups, as monotherapy and in combination with other agents. Up to now, data are insufficient to support a formal indication, and further research is needed.
CONCLUSIONS: Efforts to precisely define the homologous repair deficiency (HRD) in CRC - and eventually the subgroup of patients that are expected to benefit the most - are also underway.
OBJECTIVE: This review article aims to better clarify the role of PARP inhibitors as a treatment option in patients with metastatic CRC with alterations in the DDR pathway.
METHODS: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of PARP inhibitors in patients with metastatic CRC with homologous repair deficiency (HRD) and the correct line of therapy.
RESULTS: Current evidence supports the utilization of PARP inhibitors in CRC subgroups, as monotherapy and in combination with other agents. Up to now, data are insufficient to support a formal indication, and further research is needed.
CONCLUSIONS: Efforts to precisely define the homologous repair deficiency (HRD) in CRC - and eventually the subgroup of patients that are expected to benefit the most - are also underway.
摘要：
背景：结直肠癌（CRC）是西方世界最常见的恶性肿瘤之一，转移性疾病与不良预后相关。聚-阿培糖聚合酶（PARP）抑制剂在医学肿瘤学领域得到越来越多的关注，因为它们在DNA损伤修复（DDR）途径中预先存在的改变的恶性肿瘤中导致合成致死性。由于这些改变在CRC中经常出现，通过PARP抑制剂的靶向方法有望使这些患者受益，单独或与化疗等其他药物联合使用，免疫疗法，抗血管生成药物,和辐射。
目的：这篇综述文章旨在更好地阐明PARP抑制剂作为DDR通路改变的转移性CRC患者的治疗选择的作用。
方法：我们使用PubMed数据库检索期刊文章，纳入标准均为人类研究，这些研究表明PARP抑制剂在患有同源修复缺陷（HRD）的转移性CRC患者中的有效作用以及正确的治疗路线。
结果：目前的证据支持在CRC亚组中使用PARP抑制剂，作为单一疗法，并与其他药物联合使用。到目前为止,数据不足以支持正式的指示，需要进一步的研究。
结论：精确定义CRC中同源修复缺陷（HRD）的努力也在进行中——以及最终预期受益最大的患者亚组。
背景：DOI：dx。doi.org/10.17504/protocols.io.dm6gp3ey8vzp/v1.
目的：这篇综述文章旨在更好地阐明PARP抑制剂作为DDR通路改变的转移性CRC患者的治疗选择的作用。
方法：我们使用PubMed数据库检索期刊文章，纳入标准均为人类研究，这些研究表明PARP抑制剂在患有同源修复缺陷（HRD）的转移性CRC患者中的有效作用以及正确的治疗路线。
结果：目前的证据支持在CRC亚组中使用PARP抑制剂，作为单一疗法，并与其他药物联合使用。到目前为止,数据不足以支持正式的指示，需要进一步的研究。
结论：精确定义CRC中同源修复缺陷（HRD）的努力也在进行中——以及最终预期受益最大的患者亚组。
背景：DOI：dx。doi.org/10.17504/protocols.io.dm6gp3ey8vzp/v1.
