مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
The Role of Dihydrotestosterone in the Pathogenesis of Prostate Cancer: A Review of Molecular Mechanisms and Proposed Therapeutic Approaches
The Role of Dihydrotestosterone in the Pathogenesis of Prostate Cancer: A Review of Molecular Mechanisms and Proposed Therapeutic Approaches
Zomorrod Zalani,1Negin Bakiasay,2Issa Layali,3Pezhman Shafiei Asheghabadi,4,*
1. 1 Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2 Biology Association, Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2. 1 Department of Animal Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2 Biology Association, Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 3. 1 Department of Biochemistry and Biophysics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2 Biology Association, Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 4. 1Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Introduction: According to the statistics of the World Health Organization (WHO), cancer is one of the main causes of death in the world. In this study, we pay special attention to prostate cancer and the effect of Dihydrotestosterone (DHT) on its pathogenesis. Androgens such as testosterone and DHT are an important stimulus in the growth and development of prostate cancer, however, the molecular mechanisms involved in this process are not yet fully understood. In this study, we describe the molecular mechanisms of DHT in the pathogenesis of prostate cancer and examine the current therapeutic challenges in this field.
Methods: In order to collect useful materials and studies, it was conducted an extensive search in “PubMed” and “Google Scholar” databases and identified 21 articles that were most relevant to our topic.
Results: The development and persistence of prostate cancer is mainly related to the high expression of androgen receptor (AR) and its dysregulation. Testosterone is released from the gonads into the blood and converted to 5α-DHT by steroid-5α reductase (SRD5A) in prostate cancer, which promotes tumor growth by activating AR. Advanced prostate cancer is inhibited in the early stages by reducing the concentration of testosterone in the gonads and usually produces a therapeutic response. Recently, androgen deprivation therapy (ADT) and immunotherapy have been shown to be potential treatment options in men with metastatic prostate cancer (CaP), but androgens are usually suggested as suppressors of the immune response. Also, recent researches have introduced DHT as an increaser of macrophage cytotoxicity, which makes immunotherapy-based treatments undesirable. Also, recent evidence has shown that androgen deprivation therapy of prostate cancer with estrogen has significant cardiovascular side effects.
Conclusion: Prostate cancer is a multifactorial disease and many endogenous factors are involved in its pathogenesis, therefore, in order to provide a targeted treatment approach, it is important to further analyze the molecular mechanisms and the effects of DHT on the biogenesis of prostate cancer.