Ryohei Kozaki, Shingo Hotta, Koji Teraishi, Cuifang Li, Kenji Oritani, Tadashi Matsuda
Breast tumor kinase (Brk) is highly expressed in breast cancer and plays essential roles in tumor cell survival, proliferation, migration, and invasion. Previous studies have validated Brk as a potential therapeutic target in breast cancer using genetic knockdown and small-molecule inhibitors. However, the therapeutic potential of Brk inhibition has not been investigated in non-breast epithelial cancers. In this study, we evaluated the antitumor effects of Brk suppression in prostate, pancreatic, and head and neck cancer cell lines by employing RNA interference and a selective Brk kinase inhibitor, both in vitro and in vivo. Furthermore, in colorectal and skin cancer cell lines, we examined the combinatorial antitumor effects of Brk inhibition with epidermal growth factor receptor inhibitors, radiation, and anti-programmed cell death-1 antibody therapy. Through these studies, we demonstrate that Brk inhibitors hold significant promise as novel therapeutic agents for epithelial cancers beyond breast cancer.