Hormonal therapy and chemotherapy are currently two major treatments for prostate cancer.However, tumor cells will eventually develop resistance to these therapies.We are particularly interested in understanding the molecular mechanisms underlying drug resistance.We and others have shown that autocrine/paracrine factors produced by tumor cells may play an important role in development of drug resistance.These autocrine/paracrine factors can activate a series of protein kinase cascades that control the anti-apoptotic signaling to confer the resistance.I will present some of our data to illustrate how Src tyrosine kinase regulate the androgen receptor activity in hormone resistant prostate cancer cells and how Etk and Pim-1 kinases modulate the sensitivity of tumor cells to chemotherapeutic drugs by antagonizing tumor suppressor p53.The implications of these studies for developing more effective regimen for prostate cancer will be discussed.