Fyn: A Key Regulator of Metastasis in Prostate Cancer

My laboratory has continued to study the role of the novel molecular target, Fyn, in prostate cancer. In this second year of DoD funding we have made significant progress in defining the Fyn signaling pathway and its relationship with Met: a novel and important molecular target in several diseases including prostate cancer. Also, we have completed an important initial battery of murine studies showing an effect on dissemination: When Fyn deficient tumor cells were injected in vivo, their ability to metastasize was significantly diminished. Our studies continue to support the importance of Fyn as putative therapeutic target in advanced prostate cancer. This has become critically important given the recent report by Araujo of the long awaited phase 3 study of docetaxel with or without dasatinib, a Src-family kinase (SFK) inhibitor. The disappointing results have threatened the viability of applying SFK inhibition to the disease of prostate cancer. My group and others still believe that the completed study failed to translationally address the relevant biology of Fyn and SFKs in prostate cancer. Clinical studies with translational endpoints are now being planned with agents that effectively inhibit Fyn and Met in a variety of settings.