TAOK inhibitors for cancer therapy: current research progress and future directions

As members of the serine/threonine protein kinase family, TAOKs regulate signaling pathways such as p38 MAPK and Hippo, and participate in the processes of tumor cell proliferation, drug resistance and mitosis. TAOKs are abnormally expressed in various cancers including breast cancer, prostate cancer and pancreatic cancer, which make them promising antitumor targets. Accordingly, TAOKs inhibitors have emerged as a preferred strategy in the development of anticancer drugs. Although no TAOK inhibitors have yet entered the human clinical trial stage, several TAOK inhibitors and dual-target inhibitors demonstrated the excellent preclinical activity. This review summarizes the design strategies of TAOK inhibitors, outlines their structure-activity relationships, and discusses the challenges. Importantly, this review proposes that future directions will focus on the discovery of potent and selective TAOK inhibitors, overcoming drug resistance, developing combined treatment strategies, expanding the indications and applications to other diseases, exploring the signaling network mechanisms of TAOKs, and promoting the clinical translation. By systematically summarizing the current research progress of TAOK inhibitors, this review can provide the theoretical support and research guidance for the design of novel TAOK inhibitors, the optimization of their pharmacological properties, and the implementation of clinical translational research.