Combined treatment of Dunning R3327 rat prostatic tumor with the 5α-reductase inhibitor PNU 157706 and the antiandrogen bicalutamide

Abstract

These data show that the inhibitory effect of PNU 157706 and bicalutamide on Dunning prostatic tumor growth is additive, thus suggesting a possible role of PNU 157706 in the therapy of advanced prostate cancer, in combination with antiandrogens, to provide an effective peripheral androgen ablation therapy with minimal side effects.

Differential alterations in 5α‐reductase type 1 and type 2 levels during development and progression of prostate cancer

“…Because DHT is thought to be crucial in the development of PCa, 5aR inhibition has received attention as an option for PCa prevention. Inhibition of 5aR using compounds such as epristeride [17], turosteride [18], and PNU 157706 [19] caused reduced growth of PCa xenografts in rats. However, the most extensively studied 5aR inhibitor is finasteride.…”

Transgenic Mouse Model for Rapid Pharmacodynamic Evaluation of Antiandrogens

“…Whereas in vitro and cell-based assays are relatively straightforward, in vivo methods to assess antiandrogen activity are complex and cumbersome. For example, a typical readout is the wet weight of the ventral, lateral, and dorsal lobes of the prostate in rats treated with the compound of interest >14 days (5,6). Although the development and maintenance of these glands is exquisitely androgen dependent and accurately reflects physiologic androgen receptor function, this assay presents numerous experimental challenges that preclude evaluation of large numbers of compounds, such as the treatment time, dynamic range of the prostate weight, and number of animals required to obtain conclusive information.…”

Biochemical recurrence after definitive prostate cancer therapy. Part II: Treatment strategies for biochemical recurrence of prostate cancer*

“…The disadvantages of this therapy are a current lack of evidence that this approach prolongs survival, breast tenderness or gynecomastia; and treatment is more expensive than observation or orchiectomy [59]. Despite the lack of longterm efficacy in humans, there are animal model data that provide a rationale for the use of these therapies [62][63][64].…”