New ideas of androgen deprivation therapy for prostate cancer: new progress in clinical research of testosterone maximum control

卞晓洁; 叶定伟

doi:10.19401/j.cnki.1007-3639.2021.12.009

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New ideas of androgen deprivation therapy for prostate cancer: new progress in clinical research of testosterone maximum control

更新时间：2025-12-31

- New ideas of androgen deprivation therapy for prostate cancer: new progress in clinical research of testosterone maximum control
- China Oncology Vol. 31, Issue 12, Pages: 1209-1214(2021)
- 作者机构：
  
  复旦大学附属肿瘤医院泌尿外科，复旦大学上海医学院肿瘤学系,上海,200032
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2021.12.009
  CLC：
- Published Online：07 January 2022，
  
  Published：07 January 2021
- 稿件说明：
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卞晓洁, 叶定伟. 前列腺癌雄激素剥夺治疗的新思路——睾酮最大控制临床研究新进展[J]. 中国癌症杂志, 2021, 31(12): 1209-1214.

卞晓洁, 叶定伟. New ideas of androgen deprivation therapy for prostate cancer: new progress in clinical research of testosterone maximum control[J]. China Oncology, 2021, 31(12): 1209-1214.
卞晓洁, 叶定伟. 前列腺癌雄激素剥夺治疗的新思路——睾酮最大控制临床研究新进展[J]. 中国癌症杂志, 2021, 31(12): 1209-1214. DOI： 10.19401/j.cnki.1007-3639.2021.12.009.

卞晓洁, 叶定伟. New ideas of androgen deprivation therapy for prostate cancer: new progress in clinical research of testosterone maximum control[J]. China Oncology, 2021, 31(12): 1209-1214. DOI： 10.19401/j.cnki.1007-3639.2021.12.009.

摘要

前列腺癌是常见的男性恶性肿瘤之一，其发病率位居男性恶性肿瘤第二位。前列腺癌的发病率居于所有男性恶性肿瘤首位。中国男性的前列腺癌发病率低于欧美国家，但随着生活方式、饮食习惯的西化以及人均寿命延长，前列腺癌的发病率也呈现逐年升高的趋势。雄激素受体（androgen receptor，AR）在前列腺癌的发生、发展过程中扮演着重要角色，抑制AR信号转导通路是前列腺癌治疗的基础，比如在去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC）治疗中，使用AR拮抗剂能够竞争性结合AR并阻断内源性雄激素的结合，从而干扰雄激素依赖的细胞下游反应，阻止前列腺癌的进展。雄激素剥夺治疗（androgen deprivation therapy，ADT）是前列腺癌治疗的基石，国内专家共识中前列腺癌去势治疗有效定义的睾酮（testosterone，T）水平为低于50 ng/dL。随着研究的深入，越来越多的研究表明T低于20 ng/dL的患者临床预后更佳：T ＜ 20 ng/dL时可以诱导包括雄激素敏感和部分雄激素不敏感亚群细胞的死亡，在治疗间隙细胞增殖时可以获得雄激素高度敏感的细胞群，从而延长了去势抵抗的时间。如果不能达到T ＜ 20 ng/dL，可能会导致部分雄激素不敏感的亚群持续存在，这些亚群在再次治疗后会快速增殖，加速肿瘤向去势抵抗发展。目前控制T水平的促性腺激素释放激素激动剂（gonadotropin-releasing hormone agonist，GnRHa）的有效性和安全性在研究中和临床上均得到了明确的验证，在药物层面上提供了控制T ＜ 20 ng/dL的临床可行性。通过总结T水平与ADT新进展，探讨最大限度控制T水平与前列腺癌治疗中患者受益、药物疗效及安全性的关系。

Abstract

Prostate cancer is the most common male malignant tumor

ranking second among male malignant tumors. The incidence rate of prostate cancer is the highest in all male cancers. The incidence rate of China's prostate cancer is lower than that of western countries. However

with the westernization of lifestyle

the westernization of life habits and the prolongation of life expectancy

the incidence rate of prostate cancer is increasing year by year. Androgen receptor (AR) plays an important role in the pathophysiological mechanism of prostate cancer. Inhibiting AR signal transduction pathway is the basis of prostate cancer treatment. For example

in the treatment of castration-resistant prostate cancer (CRPC)

AR antagonists can competitively bind AR and block the binding of endogenous androgen. Thus

it interferes with the downstream response of androgen dependent cells and prevents the progression of prostate cancer. Androgen deprivation therapy (ADT) is the cornerstone in the treatment of prostate cancer. According to the consensus of domestic experts

the effective testosterone (T) level for ADT is less than 50 ng/dL. Accumulated studies have shown that patients with T ＜ 20 ng/dL have better clinical prognosis. Lower T level (less than 20 ng/dL) results in more death of androgen-sensitive and some androgen-insensitive cells. During the treatment

androgen-sensitive cell populations can be obtained

thereby prolonging the duration to castration resistance. If T ＜ 20 ng/dL cannot be achieved

some androgen-insensitive subpopulations may persist. These subpopulations will proliferate rapidly after retreatment and accelerate the progression of tumor resistance to castration. The safety and effectiveness of gonadotropin-releasing hormone agonist (GnRHa)

which controls T levels

have been verified by laboratory and clinical evidence

providing the clinical feasibility of controlling T at the level less than 20 ng/dL. This article reviewed the advances in the relationship between T level and ADT

and exhibited the drug efficacy

safety and patient benefits from the treatment of prostate cancer.

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