Zhong Shangwei, Peng Shoujiao, Chen Zihua, Chen Zhikang, Luo Jun-Li
Department of General Surgery, Xiangya Hospital, Central South University, Hunan 410008, China.
Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33459, USA.
Pharmaceutics. 2022 Feb 24;14(3):498. doi: 10.3390/pharmaceutics14030498.
Androgen deprivation therapy (ADT) is a systemic therapy for advanced prostate cancer (PCa). Although most patients initially respond to ADT, almost all cancers eventually develop castration resistance. Castration-resistant PCa (CRPC) is associated with a very poor prognosis, and the treatment of which is a serious clinical challenge. Accumulating evidence suggests that abnormal expression and activation of various kinases are associated with the emergence and maintenance of CRPC. Many efforts have been made to develop small molecule inhibitors to target the key kinases in CRPC. These inhibitors are designed to suppress the kinase activity or interrupt kinase-mediated signal pathways that are associated with PCa androgen-independent (AI) growth and CRPC development. In this review, we briefly summarize the roles of the kinases that are abnormally expressed and/or activated in CRPC and the recent advances in the development of small molecule inhibitors that target kinases for the treatment of CRPC.
雄激素剥夺疗法（ADT）是一种用于晚期前列腺癌（PCa）的全身治疗方法。尽管大多数患者最初对ADT有反应，但几乎所有癌症最终都会产生去势抵抗。去势抵抗性前列腺癌（CRPC）的预后非常差，其治疗是一项严峻的临床挑战。越来越多的证据表明，各种激酶的异常表达和激活与CRPC的出现和维持有关。人们已经做出了许多努力来开发针对CRPC关键激酶的小分子抑制剂。这些抑制剂旨在抑制激酶活性或中断与PCa雄激素非依赖性（AI）生长和CRPC发展相关的激酶介导的信号通路。在这篇综述中，我们简要总结了在CRPC中异常表达和/或激活的激酶的作用以及针对激酶治疗CRPC的小分子抑制剂开发的最新进展。
