PAK as a therapeutic target in gastric cancer.

IMPORTANCE OF THE FIELD: Gastric cancer is one of the most common causes of cancer death worldwide. P21-activated kinases (PAKs), regulators of cancer-cell signalling networks, play fundamental roles in a range of cellular processes through their binding partners or kinase substrates. AREAS COVERED IN THIS REVIEW: The complex regulation of PAKs through their upstream or downstream effectors in human cancers, especially in gastric cancer, are described and the identified inhibitors of PAKs are summarized. WHAT THE READERS WILL GAIN: The structural differences and activation mechanisms between two subgroups of PAK are described. Both groups of PAKs play complicated and important roles in human gastric cancer, which indicated a possible way for us to identify the specific inhibitors targeting PAKs for gastric cancer. TAKE HOME MESSAGE: PAKs play important roles in progression of many cancer types, the full mechanisms of PAKs in gastric cancer are still unclear. It seems there are different roles for two groups of PAKs in cancers. Group I PAKs play their functions mostly through their specific substrates, however, many binding partners that are independent of phosphorylation by group II PAKs were identified. Finding specific inhibitors of PAKs will help us discover the roles of PAKs and target these kinases in human gastric cancer.