文章：

性别因素至关重要——从胰腺癌动物模型药物疗效测试中获得的启示

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer

原文发布日期：16 May 2024

DOI: 10.3390/cancers16101901

类型: Article

开放获取: 是

英文摘要：

Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice. Male mice had less tumor infiltration of CD8-positive cells, developed bigger tumors, had more lung metastasis and a lower probability of survival compared to female mice. These more severe pathological features in male animals were accompanied by higher distress at the end of the experiment. The evaluated inhibitors BI-3406, trametinib and BKM120 showed synergistic effects in vitro. This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds.

摘要翻译： 

临床前研究很少在两种性别中测试疗法的有效性，肿瘤学领域在这方面也不例外。在一种同基因、原位、转移性胰腺导管腺癌模型中，我们评估了性别对该疾病病理特征的影响，以及一种新型小分子疗法（通过抑制KRAS:SOS1、MEK1/2和PI3K信号通路）在雄性和雌性C57BL/6J小鼠中的疗效及潜在副作用。与雌性小鼠相比，雄性小鼠肿瘤中CD8阳性细胞浸润较少，肿瘤体积更大，肺转移更多，生存概率更低。雄性动物这些更严重的病理特征伴随着实验结束时更高的痛苦程度。所评估的抑制剂BI-3406、曲美替尼和BKM120在体外显示出协同效应。这种联合疗法在雄性动物中更有效地减少了肿瘤重量，尽管两性肿瘤中的药物浓度相似。这些结果强调了性别特异性临床前研究的重要性，同时为未来使用这些测试化合物的研究提供了坚实基础。

原文链接：

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer