Targeting ACK1/TNK2 kinase to treat cancer

ACK1 is a widely expressed, multidomain cytoplasmic tyrosine kinase encoded by the TNK2 gene. 

Overexpression of ACK1 through gene amplification or its activation by interaction with other tyrosine kinases occurs during the initiation and progression of multiple cancer types, and is also seen in neuropsychiatric and autoimmmune diseases.

Aberrantly active ACK1 interacts with the immune kinase CSK which modulates immune activation, thereby making cancers resistant to immune checkpoint blockade.

ACK1 is an epigenetic imprinter that regulates the deposition of histone H4 phosphorylated on Tyr88 (pY88-H4) and H3 phosphorylated on Tyr54 (pY54-H3) at the androgen receptor and cell-cycle genes, and thus contributes to cancer progression, chemoresistance, and increased stemness.

Clinical testing of ACK1 inhibitors holds promise in anticancer therapy.

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(24)00247-5

https://sciencemission.com/ACK1TNK2-kinase:-molecular-mechanisms-and-emerging-cancer-therapeutics