PAK4 in cancer development: Emerging player and therapeutic opportunities

p21-activated kinase 4 (PAK4), a member of the serine-threonine kinase family, was initially identified as a protein kinase that functions downstream of the Rho GTPases cdc42 and Rac1. Recently, it has been proven that PAK4 not only regulates many cellular physiological processes, but also plays an important role in the occurrence and development of various cancers. Here, we provide a systematic overview of PAK4, including its structure, localization, expression and aberration, upstream regulators, and key functions in almost every aspect of cancer hallmarks, including cancer cell proliferation, invasion and metastasis, angiogenesis, metabolism reprogramming, and immune escape. Subsequently, we also discuss the existing small molecule PAK4 inhibitors according to their structure types and their potential applications in cancer treatment. We hope our systematic review will provide the most comprehensive description of the current advancements in PAK4 research and new enlightenment for the individualized diagnosis and treatment of cancer.