PAK2 as a therapeutic target in cancer: Mechanisms, challenges, and future perspectives

Abstract

P21-activated kinases (PAKs) are crucial regulators within cellular signaling pathways and have been implicated in a range of human diseases, including cancer. Among the PAK family, PAK2 is widely expressed across various tissues and has emerged as a significant driver of cancer progression. However, systematic studies on PAK2 remain limited. This review provides a comprehensive overview of PAK2's role in cancer, focusing on its involvement in processes such as angiogenesis, metastasis, cell survival, metabolism, immune response, and drug resistance. We also explore its function in key cancer signaling pathways and the potential of small-molecule inhibitors targeting PAK2 for therapeutic purposes. Despite promising preclinical data, no PAK2 inhibitors have reached clinical practice, underscoring challenges related to their specificity and therapeutic application. This review highlights the biological significance of PAK2 in cancer and its interactions with critical signaling pathways, offering valuable insights for future research. We also discuss the major obstacles in developing PAK inhibitors and propose strategies to overcome these barriers, paving the way for their clinical translation.