用于治疗前列腺癌的BH3模拟物
BH3 Mimetics for the Treatment of Prostate Cancer.
作者信息
Wolf Philipp
机构信息
Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of FreiburgFreiburg, Germany.
出版信息
Front Pharmacol. 2017 Aug 18;8:557. doi: 10.3389/fphar.2017.00557. eCollection 2017.
Abstract
Despite improved diagnostic and therapeutic intervention, advanced prostate cancer (PC) remains incurable. The acquired resistance of PC cells to current treatment protocols has been traced to apoptosis resistance based on the upregulation of anti-apoptotic proteins of the Bcl-2 family. The use of BH3 mimetics, mimicking pro-apoptotic activator or sensitizer proteins of the intrinsic apoptotic pathway, is therefore a promising treatment strategy. The present review gives an overview of preclinical and clinical studies with pan- and specific BH3 mimetics as sensitizers for cell death and gives an outlook how they could be effectively used for the therapy of advanced PC in future.
摘要
尽管诊断和治疗干预有所改进，但晚期前列腺癌（PC）仍然无法治愈。PC细胞对当前治疗方案产生的获得性耐药性已被追溯到基于Bcl-2家族抗凋亡蛋白上调的凋亡抗性。因此，使用BH3模拟物，即模拟内源性凋亡途径的促凋亡激活剂或敏化剂蛋白，是一种有前景的治疗策略。本综述概述了使用泛BH3模拟物和特异性BH3模拟物作为细胞死亡敏化剂的临床前和临床研究，并展望了它们未来如何能有效地用于晚期PC的治疗。
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Transl Androl Urol. 2017 Apr;6(2):315-316. doi: 10.21037/tau.2017.02.01.
2
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Clin Cancer Res. 2016 Sep 15;22(18):4698-711. doi: 10.1158/1078-0432.CCR-15-2827. Epub 2016 Apr 28.
3
Major apoptotic mechanisms and genes involved in apoptosis.
Tumour Biol. 2016 Jul;37(7):8471-86. doi: 10.1007/s13277-016-5035-9. Epub 2016 Apr 9.
4
Pseudomonas Exotoxin A: optimized by evolution for effective killing.
Front Microbiol. 2015 Sep 15;6:963. doi: 10.3389/fmicb.2015.00963. eCollection 2015.
5
Mcl-1 protects prostate cancer cells from cell death mediated by chemotherapy-induced DNA damage.
Oncoscience. 2015 Sep 1;2(8):703-15. doi: 10.18632/oncoscience.231. eCollection 2015.
6
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.
N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5.
7
Androgen deprivation of prostate cancer: Leading to a therapeutic dead end.
Cancer Lett. 2015 Oct 10;367(1):12-7. doi: 10.1016/j.canlet.2015.06.021. Epub 2015 Jul 13.
8
New dimension in therapeutic targeting of BCL-2 family proteins.
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9
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10
Mechanistic rationale for MCL1 inhibition during androgen deprivation therapy.
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