Recent progress on FAK inhibitors with dual targeting capabilities for cancer treatment
Xianbo Wu, Jie Wang, Qi Liang, Rongsheng Tong, Jianli Huang, Xinwei Yang, Yihua Xu, Wenjing Wang, Minghan Sun, Jianyou Shi
Abstract
Focal adhesion kinase (FAK, also known as PTK2) is a tyrosine kinase that regulates integrin and growth factor signaling pathways and is involved in the migration, proliferation and survival of cancer cells. FAK is a promising target for cancer treatment. Many small molecule FAK inhibitors have been identified and proven in both preclinical and clinical studies to be effective inhibitors of tumor growth and metastasis. There are many signaling pathways, such as those involving FAK, Src, AKT, MAPK, PI3K, and EGFR/HER-2, that provide survival signals in cancer cells. Dual inhibitors that simultaneously block FAK and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, the antitumor mechanisms and research status of dual inhibitors of FAK and other targets, such as Pyk2, IGF-IR, ALK, VEGFR-3, JAK2, EGFR, S6K1, and HDAC2, are summarized, providing new ideas for the development of effective FAK dual-target preparations.