Abbasi Ali, Movahedpour Ahmad, Amiri Ahmad, Najaf Mohamad Samare, Mostafavi-Pour Zohreh
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Curr Mol Med. 2021;21(4):332-346. doi: 10.2174/1566524020666200903120344.
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 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 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.
前列腺癌（PC）是全球男性中最常见的癌症。雄激素剥夺疗法（ADT）是PC治疗的初始治疗方法之一，多种药物可用于PC治疗的常规激素治疗。然而，PC细胞可以通过不同机制存活并继续生长，这导致它们对常用治疗产生抗性，即恩杂鲁胺。达罗他胺（ODM-201）是一种具有新化学结构的第二代雄激素受体（AR）抑制剂，对AR具有高亲和力。达罗他胺不会穿过血脑屏障，因此降低了癫痫发作的可能性。达罗他胺还可以抑制几种AR突变变体（F877L、F877L/T878A和H875Y/T878A）的转录活性，这些变体对恩杂鲁胺耐药。在本综述中，我们回顾了不同研究的结果：体外、动物模型以及1期、2期和3期临床试验（ARADES、ARAFOR和ARAMIS）。我们将讨论正在进行的全球2期和3期临床试验（ARASENS和ODENZA），以证明在不同患者群体中使用达罗他胺的优势。达罗他胺在抑制MR49F（恩杂鲁胺耐药PC细胞）和VCaP（去势抵抗性PC细胞）细胞系的生长以及AR的转录活性方面显示出高潜力。与恩杂鲁胺相比，所需的达罗他胺剂量更少。在动物模型中，该药物具有显著的抗肿瘤活性，对血清睾酮水平无影响。达罗他胺在不同研究中证明了其安全性和有效性，几乎在所有患者中都具有良好的耐受性。
