Prostate cancer (PC) is known as the most frequent cancer among men in the
world. Androgen Deprivation Therapy (ADT) is one of the initial treatment approaches in
the PC therapy and various drugs can be used in routine Hormonal therapy for PC
therapy. Nevertheless, PC cells can survive and continue their growth via different
mechanisms which lead to their resistance to common treatments i.e., Enzalutamide.
olutamide (ODM-201) is a second-generation androgen receptor (AR) inhibitor with a
new chemical structure and has a high affinity to the AR. Darolutamide does not cross
the blood-brain barrier and for this reason, reduces the possibility of seizures.
Darolutamide can also inhibit the transcriptional activity of several AR mutant variants
(F877L, F877L/T878A, and H875Y/T878A), which are Enzalutamide resistant. In this
review, we reviewed the results of different studies: in vitro, animal model and phase 1,
2 and 3 clinical trials (ARADES, ARAFOR and ARAMIS). We shall discuss worldwide
phase 2 and 3 clinical trials (ARASENS and ODENZA) that are in progress, in order to
demonstrate the advantages of Darolutamide consumption in different groups of
Darolutamide has shown high potential in inhibiting the growth of MR49F (Enzalutamide
resistant PC cells) and VCaP (Castration-resistant PC cells) cell lines and transcriptional
activities of AR. Fewer doses of Darolutamide are needed compared to Enzalutamide.
The drug had significant anti-tumor activity and no effect on serum testosterone levels in
animal models. Darolutamide demonstrates its safety and efficacy in different studies
and was well tolerated nearly in all of the patients.