Proteomic analysis of FAK function in human pancreatic cancer

粘着斑激酶（FAK）蛋白在多种恶性肿瘤中上调，包括胰腺癌。它的表达与肿瘤促炎有关。此外，FAK的抑制剂已经进展到临床试验的第二阶段，许多制药公司正在探索其作为免疫原性剂的功能。这些研究是基于最近的发现，其中FAK抑制干扰素γ（IFN γ）应答，与癌症（包括胰腺癌）的免疫抗性密切相关。这种耐药性的完整机制仍然未知，本研究旨在解决它。该项目旨在使用一组约30个胰腺癌患者来源的细胞系研究FAK的功能，重点是IFN γ调节及其对抗原库的影响。该研究的主要目的是确定临床相关的蛋白质组特征，并允许患者分层，从而确定最有可能从FAK抑制治疗中获益的亚组。用于实现这些目标的方法将取决于定量蛋白质组学和生物信息学分析，结合湿和干实验室工作。

Focal Adhesion Kinase (FAK) protein is being upregulated in a variety of malignancies, including pancreatic cancer. It has been shown that its expression is related to the tumour promoting inflammation. Moreover, the inhibitors of FAK have progressed onto the second stage of clinical trials, with numerous pharmaceutical companies exploring its function as an immunogenic agent. The investigations are based on the recent findings, where FAK suppresses interferon y (IFNy) response, closely associated with immunoresistance of carcinomas, including Pancreatic Cancer. The full mechanism of this resistance remains unknown, and this study was constructed to address it. The project aims to investigate FAK's function using a panel of ~30 patient-derived cell lines of pancreatic cancer, with the emphasis on the IFNy regulation and its effect on the antigen repertoire presented. The major aim of the study is to determine the proteomic signature that would be clinically relevant, and would allow patients' stratification leading to the identification of subgroups most likely to benefit from FAK inhibition treatment. The approach used to address those aims would depend on the quantitative proteomics and bioinformatic analyses combining both, wet and dry laboratory work.