Enzalutamide/enzalutamide effects and efficacy

Enzalutamide/Enzalutamide (Enzalutamide) is a second-generation antiandrogen that blocks the activity of androgens and the androgen receptor (AR) in prostate cancer. Due to the normal physiological functions of prostate cells, AR activity is closely related to prostate cancer progression, which provides a theoretical basis for androgen deprivation therapy (ADT).

However, resistance eventually develops within 2-3 years after initiation of ADT due to the accumulation of mutations, including constitutively active mutations, AR overexpression, and changes in AR splice variants. Enzalutamidewas therefore designed to take advantage of these mutations. In vitro experiments in the human prostate cancer cell line VCaP showed that enzalutamide inhibited cell growth and induced apoptosis, whereas other antiandrogens such as bicalutamide did not.

Enzalutamideis a competitive androgen receptor inhibitor with triple inhibitory effects on the androgen signaling pathway, but has no significantAR agonist activity. It inhibits the binding of androgens to their receptors, androgen receptor nuclear translocation and subsequent interaction with chromosomal DNA to upregulate oncogenes. The binding affinity of enzalutamide to AR is 5 to 8 times higher than that of first-generation antiandrogens (such as bicalutamide), and only 2 to 3 times lower than the natural ligand dihydrotestosterone. Molecular docking showed that the binding of enzalutamide to the ligand-binding domain ofAR was significantly different from the binding of androgen receptor.

Clinical trials in patients with prostate cancer have shown that enzalutamide can cause a decrease in serum prostate-specific antigen (PSA) for at least 12 weeks, although this response may be transient and therefore lead to resistance to enzalutamide. Patients who received enzalutamide also had a 37% lower risk of death compared with placebo.