Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models
Annual rept. 14 Jan 2004-13 Jan 2005
NORTHWESTERN UNIV EVANSTON IL
Pagination or Media Count:
One critically important problem in prostate cancer research is to find new approaches to slow down the transition of prostate cancer from an androgen-dependent state to a lethal androgen-refractory state. Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells. However, the advantage of inducing differentiation of prostate cancer cells by intermittent recovery of androgens is compromised by the disadvantage of androgenic induction of prostate cancer cell proliferation. The biologically most active androgen is dihydrotestosterone DHT, which is converted from testosterone T by 5alpha-reductase. Our recent studies showed that T is more potent than DHT in enhancing differentiation but weaker in stimulating proliferation, which led to our hypothesis that intermittent androgen suppression IAS can be enhanced by finasteride, an inhibitor of T to DHT conversion. We have tested our hypothesis using LNCaP xenograft tumors in nude mice. Our experiments showed that finasteride administration during IAS significantly reduced tumor growth rate and prolonged the life of nude mice bearing LNCaP tumors.
- Medicine and Medical Research