临床前研究很少测试治疗方法对男女的疗效。肿瘤学领域在这方面也不例外。在同基因、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，以及抑制 KRAS:SOS1、MEK1 的新型小分子疗法的疗效和可能的不良副作用雄性和雌性 C57BL/6J 小鼠中的 /2 和 PI3K 信号传导。与雌性小鼠相比，雄性小鼠的 CD8 阳性细胞肿瘤浸润较少，肿瘤较大，肺转移较多，存活率较低。雄性动物中这些更严重的病理特征在实验结束时伴随着更高的痛苦。所评估的抑制剂BI-3406、曲美替尼和BKM120在体外表现出协同作用。这种组合疗法在雄性动物中更有效地降低了肿瘤重量，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，同时为未来的测试化合物研究提供了坚实的基础。

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.