Kinase inhibitors in prostate cancer.

Prostate cancer is a significant public health problem around the world. Once a patient has disease that is no longer addressable by local means, the cancer is considered incurable. Therapeutic goals at this point include not only extension of survival but also alteration of the natural history which may otherwise lead to significant pain and morbidity from the disease process- all related to metastases. While effective systemic therapies do currently exist, their roles are considered limited for many patients. Given the overwhelming incidence and annual mortality figures related to prostate cancer, there continues to be an urgent need for therapeutic advances. Protein kinases have emerged as "druggable" therapeutic targets as they control a multitude of basic cellular activities, including growth, survival, proliferation, differentiation and apoptosis. Several of these kinases have oncogenic properties as in the setting of malignancy they may be overactive and/or dysregulated leading to the excessive proliferation and motility typical of cancer cells. Small molecule inhibitors have shown efficacy in several tumor models and are actively being studied in prostate cancer. This review summarizes historical and contemporary studies evaluating kinase inhibitors in the treatment of prostate cancer.