The evolving landscape of protein kinases in breast cancer: clinical implications.

Dysfunction of protein kinases has been associated with the development of the various molecular subtypes of breast cancer. The best example is the known role of HER2 in the tumorigenesis of a proportion of breast tumors. In this article, we review the state of the art knowledge on protein kinases involved in breast cancer. Special attention is given to those that are potentially druggable and those for which targeted agents are currently under clinical evaluation. Options for targeted drug combinations will be discussed, as well as the optimal way to integrate new kinase inhibitors in the clinical armamentarium to fight breast cancer. We will review recent results from clinical studies with agents targeting different kinases involved in the pathophysiology of breast cancer. In addition, we will evaluate the clinical development of kinase inhibitors to identify areas of knowledge that could be explored in future preclinical and clinical studies.