title: Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer.
abstract: P21-activated kinases (PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group I (PAK1-3) and group II (PAK4-6). Focus is currently shifting from group I PAKs to group II PAKs. Group II PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group II PAKs have become popular potential drug target candidates. However, few group II PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and "drug-like" properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group II PAKs, the importance of group II PAKs in the development and progression of gastrointestinal cancer, and small-molecule inhibitors of group II PAKs for the treatment of cancer.
authors.affiliation: Yang-Guang Shao, Ke Ning, Feng Li, Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, Liaoning Province, China.
authors.forename: Yang-Guang
authors.initials: YG
authors.lastname: Shao
authors.affiliation: Yang-Guang Shao, Ke Ning, Feng Li, Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, Liaoning Province, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ning
authors.affiliation: Yang-Guang Shao, Ke Ning, Feng Li, Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, Liaoning Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C116367:PAK4 protein, human; C443802:PAK5 protein, human; C429007:PAK6 protein, human; D054462:p21-Activated Kinases
keywords: Drug target; Gastrointestinal cancer; Group II p21-activated kinases; PAK4 inhibitor; Signaling pathway
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