Department of Surgery, Austin Precinct, The University of Melbourne, 145 Studley Rd, Heidelberg, VIC, 3084, Australia.
Department of Surgery, Austin Precinct, The University of Melbourne, 145 Studley Rd, Heidelberg, VIC, 3084, Australia; Department of Hepatopancreatic-Biliary Surgery, Austin Health, 145 Studley Rd, Heidelberg, VIC, 3084, Australia.
Cancer Lett. 2022 Nov 1;548:215868. doi: 10.1016/j.canlet.2022.215868. Epub 2022 Aug 24.
Pancreatic Ductal Adenocarcinoma (PDA) is one of the most lethal types of cancer with a dismal prognosis. KRAS mutation is a commonly identified oncogene in PDA tumorigenesis and P21-activated kinases (PAKs) are its downstream mediator. While PAK1 is more well-studied, PAK4 also attracted increasing interest. In PDA, PAK inhibition not only reduces cancer cell viability but also sensitises it to chemotherapy. While PDA remains resistant to existing immunotherapies, PAK inhibition has been shown to increase cancer immunogenicity of melanoma, glioblastoma and PDA. Furthermore, autophagy plays an important role in PDA immune evasion, and accumulating evidence has pointed to a connection between PAK and cancer cell autophagy. In this literature review, we aim to summarize currently available studies that have assessed the potential connection between PAK, autophagy and immune evasion in PDA biology to guide future research.
胰腺导管腺癌（PDA）是预后最差的致命癌症类型之一。KRAS 突变是 PDA 肿瘤发生中的常见致癌基因，而 P21 激活激酶（PAKs）是其下游介质。虽然 PAK1 的研究更为深入，但 PAK4 也引起了越来越多的关注。在 PDA 中，PAK 抑制不仅降低了癌细胞的活力，而且还使其对化疗敏感。虽然 PDA 仍然对现有的免疫疗法有抗性，但 PAK 抑制已被证明可以增加黑色素瘤、神经胶质瘤和 PDA 的癌症免疫原性。此外，自噬在 PDA 的免疫逃避中起着重要作用，越来越多的证据表明 PAK 与癌细胞自噬之间存在联系。在这篇文献综述中，我们旨在总结目前评估 PAK、自噬和免疫逃避之间潜在联系的研究，以指导未来的研究。
