Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology

Abstract

Activated Cdc42-associated kinase 1 (ACK1) is an intracellular non-receptor tyrosine kinase referred to as TNK2, which is considered as an oncogene and therapeutic target in various cancers including breast cancer, non-small-cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and many others. Oncogenic non-receptor tyrosine kinase mutations occur either due to point mutations, duplications or insertions and deletions, or by involving in the development of a fusion gene resulting from a chromosomal rearrangement. ACK1 is involved with multiple signaling pathways of tumor progression. With these signaling networks, ACK1 participates in cell survival, invasion, migration, and tumorigenesis that are strongly related to the prognosis and clinicopathology of cancers. Previous studies predicted that ACK1 is a carcinogenic factor and blockage of ACK1 inhibits cancer cell survival, proliferation, migration, and radiation resistance. FDA has approved many multi-kinase inhibitors as therapeutic drugs that show good inhibitory activity not against ACK1 but also towards multiple targets. As ACK1 is a key target for other neurological diseases, inflammation, and immunological diseases also, so the studies on these inhibitors not only provide potential strategies for the treatment of cancers that require simultaneous targeting of multiple targets but also can be used in drug repurposing for other diseases.