联合放射治疗靶向胰腺癌 DNA 修复：临床前研究的系统评价。
Targeting DNA repair in combination with radiotherapy in pancreatic cancer: A systematic review of preclinical studies.
机构信息
Institut de Cancérologie Strasbourg Europe, Radiobiology Laboratory, Université de Strasbourg, Centre Paul Strauss, 3 rue de la porte de l'Hôpital, 67000, Strasbourg, France; Institut de Cancérologie Strasbourg Europe, Department de Radiation Oncology, 17 rue Albert Calmette, 67200, Strasbourg, France.
Institut de Radiothérapie des Hautes Energies, rue Lautréamont, 93000 Bobigny, France.
出版信息
Crit Rev Oncol Hematol. 2020 Sep;153:103060. doi: 10.1016/j.critrevonc.2020.103060. Epub 2020 Jul 11.
BACKGROUND
Current research that combines radiation with targeted therapy may dramatically improve prognosis of pancreatic ductal adenocarcinoma (PDAC). We investigated preclinical outcomes of DNA repair inhibitor targeted therapy associated with radiotherapy.
METHODS
We searched Pubmed database to identify publications assessing DNA damage targeted therapies in preclinical models of PDACin vitro and in vivo. Standard enhancement ratio, median survival and growth delay were extracted.
RESULTS
We identified fourteen publications using DNA repair targeted therapies in preclinical models of PDAC. Ten publications comprising twenty-eight experiments evaluated radiosensitization with different DNA repair inhibitors in vitro and displayed cell killing by a factor of 1.35 ± 0.047. Moreover, 86 % (24/28) of in vitro experiments showed radiosensitization with DNA damage response inhibitor. However, only 60 % (9/15) of the in vivo experiments presented radiosensitization effects.
CONCLUSION
DNA repair targeted therapies use promising radiosensitizers for PDAC and could successfully be translated into clinical trials.
背景
目前将辐射与靶向治疗相结合的研究可能会显著改善胰腺导管腺癌（PDAC）的预后。我们研究了与放射治疗相关的 DNA 修复抑制剂靶向治疗的临床前结果。
方法
我们在 Pubmed 数据库中检索了评估 PDAC 的体外和体内临床前模型中 DNA 靶向治疗的研究。提取标准增强比、中位生存期和生长延迟。
结果
我们在 PDAC 的临床前模型中使用了 14 种 DNA 修复靶向治疗药物。10 项研究共包含 28 项实验，评估了不同 DNA 修复抑制剂在体外的放射增敏作用，显示细胞杀伤率为 1.35±0.047。此外，86%（24/28）的体外实验显示 DNA 损伤反应抑制剂具有放射增敏作用。然而，只有 60%（9/15）的体内实验显示出放射增敏作用。
结论
DNA 修复靶向治疗为 PDAC 提供了有前途的放射增敏剂，并成功转化为临床试验。
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