The Brk protein tyrosine kinase as a therapeutic target in cancer: opportunities and challenges.

Brk is an intracellular protein tyrosine kinase that is significantly overexpressed in a majority of breast tumors, while being detected at appreciable levels in only a limited range of adult tissues that does not include the mammary gland. It has recently been demonstrated to have a role in promoting the proliferation of carcinoma cells, one that it is unlikely to perform in normal adult cells, and it therefore represents an exciting target for the development of novel cancer therapies based on specifically or selectively interfering with its functions. The strategy of pharmaceutical kinase inhibition is clinically proven and widely pursued in oncology programmes directed at a variety of tumor types. However, a potentially kinase-independent role for Brk in regulating proliferation suggests that alternative approaches, such as inhibiting protein-protein interactions, may prove more successful. Further research into Brk's signaling functions will underpin progress towards turning the potential suggested by these observations into rational drug discovery, from which a large number of patients stand to benefit.