by Leigh MacMillan
Despite the success of anti-androgen treatment for metastatic prostate cancer, nearly all patients will eventually progress to castration-resistant prostate cancer (CRPC).
Ren Jie Jin, PhD, and colleagues previously found that long-term anti-androgen treatment increases the expression of the neuroendocrine hormone, GRP, and its receptor, GRP-R, in prostate cancer cells. They showed that GRP/GRP-R signaling promotes the expression of androgen receptor splice variants (which are active in the presence of anti-androgen drugs) and cancer progression to CRPC.
In studies reported in Translational Oncology, they now demonstrate that blocking GRP-R signaling with a selective antagonist efficiently inhibits the expression of androgen receptor splice variants and sensitizes CRPC cells to anti-androgen treatment. In animal models, combining the GRP-R antagonist with anti-androgen treatment slowed the growth of both CRPC and therapy-induced neuroendocrine prostate cancer.
The findings support the potential of this combination therapy as a new approach for treating CRPC.
This research was supported by the Ferring Innovation Grant from the Ferring Research Institute and by the W. L. Bray Endowment.
