Drugs Targeting Src Kinase. Src family kinases are overexpressed in prostate cancer, and Src inhibition reduces cancer cell proliferation, adhesion, invasion and migration.
Dasatinib is an oral Bcr/Abl inhibitor that also inhibits the Src family of kinases. Although preliminary studies provided a rationale for use of dasatinib in mCRPCand early clinical trials suggested that the combination of dasatinib plus docetaxel had acceptable safety and activity, the Phase III results suggest that this combination will not be pursued further. READY is one of a string of trials that fail to show an advantage for the addition of newer agents to docetaxel. The addition of dasatinib to standard therapy with docetaxel failed to improve survival and most other clinical end points in men with metastatic castration-resistant prostate cancer (mCRPC) in the Phase III READY trial, Araujo et al. reported at the 2013 Genitourinary (GU) Cancers Symposium.
Drugs Targeting Prostate-specific Membrane Antigen (PSMA). PSMA, a highly specific antigen of prostate epithelial cell membrane, is eventually overexpressed in all prostate cancers. The mAb J591 features high affinity binding to the PSMA. Two Phase I studies defined the maximum tolerated dose and showed preliminary evidence of antineoplastic activity.