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. Darolutamide (ODM-201) is a second-generation androgen receptor (AR) inhibitor with a new chemical structure and has a high affinity to the AR. Darolutamide doesn’t cross the bloodbrain barrier, for this reason, reduces the possibility of seizures. Darolutamide also can 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 patients.
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 is needed compared to Enzalutamide. The drug had significant anti-tumor activity and had 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.
Keywords: Prostate cancer, Darolutamide, ODM-201, hormonal therapy, Castrate-resistant prostate cancer, Androgen receptor
inhibitor, second-generation androgen receptor inhibitor
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