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双相雄激素疗法:当过量燃料扑灭火焰时。

Bipolar Androgen Therapy: When Excess Fuel Extinguishes the Fire.

作者信息

Nabavi Nima, Mahdavi Seied Rabi, Ardalan Mohammad Afshar, Chamanara Mohsen, Mosaed Reza, Lara Aline, Bastos Diogo, Harsini Sara, Askari Emran, Velho Pedro Isaacsson, Bagheri Hamed

机构信息

Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran.

Radiation Sciences Research Center, AJA University of Medical Sciences, Tehran 14117-18541, Iran.

出版信息

Biomedicines. 2023 Jul 24;11(7):2084. doi: 10.3390/biomedicines11072084.

Abstract

Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.

摘要

雄激素剥夺疗法(ADT)仍然是晚期前列腺癌治疗的基石。然而,向去势抵抗性前列腺癌的进展是不可避免的,因为癌细胞会重新激活雄激素受体信号,并通过雄激素受体的自我调节来适应去势状态。此外,使用恩杂鲁胺和醋酸阿比特龙等新型激素药物进行一线治疗可能会导致长期毒性,并可能通过“达尔文式”的治疗诱导压力促使雄激素受体非依赖性细胞的产生。因此,开发新的策略来克服这些挑战至关重要。双相雄激素疗法(BAT)就是基于这样的研究而设计的一种方法,这些研究表明超生理水平的睾酮对前列腺癌生长具有矛盾的抑制作用,这种作用是通过多种协同作用的机制实现的。BAT包括在一个月的时间内使睾酮水平在超生理水平和接近去势水平之间快速交替,这是通过每月肌肉注射睾酮并同时进行ADT来实现的。BAT有效且耐受性良好,可改善生活质量,并可能使患者在疾病进展后对先前的激素疗法重新敏感。通过探索BAT的机制和临床证据,本综述旨在阐明其作为一种有前景的前列腺癌治疗新方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ee0/10377678/1844dc63f1ca/biomedicines-11-02084-g001.jpg

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