Elucidating the mechanism behind prostate cancer progression resulting from oxidative stress and its application to the clinical setting

Although it has been well known that oxidative stress promotes prostate carcinogenesis, the role of oxidative stress in the progression of prostate cancer, especially in castration-resistant progression, has remained obscure. Accordingly, we attempted to elucidate its mechanism and apply our findings to the clinical setting. To date we have been able to show that; (i) androgen-deprivation therapy induces oxidative stress in prostate cancer, and (ii) oxidative stress up-regulates the oncogenic transcription factors, Twistl and Y-box-binding protein-1 (YB-1), resulting in androgen receptor (AR) induction as well as activated AR signaling through the AR cofactor and intracellular signaling pathway, which contribute to castration-resistant progression. As regards application to the clinical setting, we have revealed promising results of antioxidant therapy as well as Twistl and YB-l-targeting therapies against prostate cancer combined with androgen-deprivation therapy. In conclusion, our results suggest that castration-resistant prostate cancer may be derived from pathways that activate invasion and metastasis by Twistl and resist cell death by YB-1, which can be reversed through the inhibition of these pathways.