ACK1及其小分子抑制剂在肿瘤发生发展中的研究进展

Research Progress on ACK1 and Its Small Molecule Inhibitors in Tumor Occurrence and Development

ACK1 (活化的Cdc42相关激酶1)属于非受体酪氨酸激酶,是小G蛋白Cdc42的效应蛋白,可以被多种细胞外生长因子如EGF、PDGF和TGF-β激活。在癌症中,ACK1的基因扩增和过表达与肺癌、卵巢癌和前列腺癌等多种恶性肿瘤的不良预后和转移表型相关。针对ACK1的研究表明,通过开发针对ACK1的高效选择性小分子抑制剂,可为癌症治疗提供新的候选药物。本综述对ACK1激活方式及其在肿瘤发生发展中的作用进行了扼要描述,阐述了ACK1的小分子抑制剂的最新研究进展,并讨论和展望了这些抑制剂在临床前研究中的应用潜力。

ACK1 (activated Cdc42-associated kinase 1) is a non-receptor tyrosine kinase and an effector protein for the small G protein Cdc42, which can be activated by various extracellular growth factors such as EGF, PDGF, and TGF-β. In cancer, the amplification and over-expression of ACK1 gene are associated with poor prognosis and metastatic phenotype in various malignant tumors such as lung cancer, ovarian cancer, and prostate cancer. Research on ACK1 suggests that developing efficient and selective small molecule inhibitors targeting ACK1 may provide new candidate drugs for cancer treatment. This review provides a brief description of the activation mode of ACK1 and its role in tumor development, elucidates the latest research progress on small molecule inhibitors of ACK1, and discusses and prospects the potential application of these inhibitors in preclinical research.