Treatment of pancreatic cancer by combination therapy with oncolytic coxsackie B3 virus PD-H-375TS, focal adhesion kinase inhibitors and checkpoint inhibitors

胰腺癌目前是所有癌症中存活率最低的。目前，100名被诊断为胰腺癌的患者中只有8人存活超过5年。免疫疗法和靶向疗法是新的治疗概念，人们对提高治疗成功率寄予厚望。这些包括溶瘤病毒、局灶黏附激酶抑制剂（FAKi）和检查点抑制剂。在我们的前期工作中，我们已经能够证明我们开发的溶解性柯萨奇病毒B3变体PD-H在体外可以感染和破坏胰腺癌细胞系，并在体内抑制胰腺肿瘤的生长。此外，我们可以证明在胰腺癌细胞中，FAK的促增殖作用可以被FAKi抑制。该项目的目的是确定PD-H- 375ts（第二代PD-H）、FAKi和检查点抑制剂联合使用的治疗潜力，并阐明促进治疗成功的机制。该研究将在具有原位胰腺肿瘤的同基因胰腺肿瘤模型中进行。通过我们的工作，我们希望为改善胰腺癌的治疗选择做出贡献。

Pancreatic cancer currently has the lowest survival rate of all cancers. Currently, only 8 out of 100 patients diagnosed with pancreatic cancer survive more than 5 years. Immunotherapies and targeted therapies are among the new treatment concepts on which great hopes are pinned for improving therapeutic success. These include oncolytic viruses, focal adhesion kinase inhibitors (FAKi) and checkpoint inhibitors. In our preliminary work, we have been able to show that the oncolytic coxsackievirus B3 variant PD-H that we developed can infect and destroy pancreatic cancer cell lines in vitro and inhibit the growth of pancreatic tumors in vivo. Furthermore, we could show that in pancreatic cancer cells the proliferation-promoting effect of FAK can be inhibited by an FAKi. The aim of the project is to determine the therapeutic potential of a combination of PD-H-375TS (second generation PD-H), FAKi and checkpoint inhibitors and to elucidate mechanisms contributing to therapeutic success. The studies will be performed in syngeneic pancreatic tumor models with orthotopic pancreas tumors. With our work we hope to contribute to the improvement of therapeutic options in pancreatic cancer.