期刊
CANCER LETTERS
卷 548, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2022.215868
关键词
Pancreatic cancer; P21 activated kinase; Autophagy; Immune evasion
类别
资金
- Pancare Foundation
- Austin Medical Research Foundation [HH-2021, MN-2020]
- MDHS (Medicine Dental Health Science, University of Melbourne) [MN2020, HH and CA 2021]
Pancreatic Ductal Adenocarcinoma (PDA) is a deadly cancer with KRAS mutation as a common oncogene. P21-activated kinases (PAKs) are downstream mediators of KRAS and play a role in PDA tumorigenesis. Inhibiting PAK reduces cancer cell viability and sensitizes them to chemotherapy. PAK inhibition also increases cancer immunogenicity in melanoma, glioblastoma, and PDA. Autophagy is important in PDA immune evasion and there is a connection between PAK and cancer cell autophagy.
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.
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