Castration-resistant prostate cancer: Targeting androgen metabolic pathways in recurrent disease
Mostaghel EA et al. - In a review of androgen metabolic pathways in recurrent castration-resistant prostate cancer (PC), targeting these metabolic enzymes either individually or using combinations of agents to inhibit testicular, adrenal, and intracrine sources may provide enhanced clinical responses in both localized and metastatic disease. Methods- Evidence suggests that despite testicular androgen ablation, residual androgens, likely of adrenal—though potentially of prostatic—origin, play a critical role in progression of PC to recurrent castration-resistant disease.
- Reassessment of the concept of total androgen deprivation is warranted.
- Current treatment strategies may not only lack optimal efficacy, but may actually contribute to selection of neoplastic clones adapted to exist and proliferate in a low (but not zero) androgen environment.
- Adequacy of androgen receptor (AR) pathway inhibition cannot be surmised from serum or plasma androgen levels, but must be ascertained at the tissue and molecular level prior to drawing conclusions regarding clinical efficacy or failure.
Results- Recent studies indicate that PCs undergo an adaptive response to castration that is associated with the up-regulation of transcripts encoding enzymes involved in the biosynthesis of androgens.
[more...]
|
|
|
