去势抵抗性前列腺癌中对雄激素受体靶向药物获得性耐药的机制
Mechanisms of acquired resistance to androgen receptor targeting drugs in castration-resistant prostate cancer.
作者信息
Chism David D, De Silva Dinuka, Whang Young E
机构信息
Department of Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
出版信息
Expert Rev Anticancer Ther. 2014 Nov;14(11):1369-78. doi: 10.1586/14737140.2014.928594. Epub 2014 Jun 13.
Abstract
After initial response to androgen receptor (AR) targeting drugs abiraterone or enzalutamide, most patients develop progressive disease and therefore, castration resistant prostate cancer remains a terminal disease. Multiple mechanisms underlying acquired resistance have been postulated. Intratumoral androgen synthesis may resume after abiraterone treatment. A point mutation in the ligand-binding domain of AR may confer resistance to enzalutamide. Emergence of AR splice variants lacking the ligand-binding domain may mediate resistance to abiraterone and enzalutamide. Steroid receptors such as glucocorticoid receptor may substitute for AR. Drugs with novel mechanisms of action or combination therapy, along with biomarkers for patient selection, may be needed to improve the therapy of castration resistant prostate cancer.
摘要
在对雄激素受体（AR）靶向药物阿比特龙或恩杂鲁胺产生初始反应后，大多数患者会出现疾病进展，因此，去势抵抗性前列腺癌仍然是一种终末期疾病。已经提出了多种获得性耐药的潜在机制。阿比特龙治疗后肿瘤内雄激素合成可能会恢复。AR配体结合域的点突变可能导致对恩杂鲁胺耐药。缺乏配体结合域的AR剪接变体的出现可能介导对阿比特龙和恩杂鲁胺的耐药。诸如糖皮质激素受体等类固醇受体可能替代AR。可能需要具有新作用机制的药物或联合治疗，以及用于患者选择的生物标志物，以改善去势抵抗性前列腺癌的治疗。
相似文献
1
Mechanisms of acquired resistance to androgen receptor targeting drugs in castration-resistant prostate cancer.去势抵抗性前列腺癌中对雄激素受体靶向药物获得性耐药的机制
Expert Rev Anticancer Ther. 2014 Nov;14(11):1369-78. doi: 10.1586/14737140.2014.928594. Epub 2014 Jun 13.
2
Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer.循环肿瘤细胞中 AR-V7 的表达并不排除去势抵抗性前列腺癌患者对下一代雄激素剥夺治疗的反应。
Eur Urol. 2017 Jan;71(1):1-3. doi: 10.1016/j.eururo.2016.07.021. Epub 2016 Jul 26.
3
Androgen receptor targeting drugs in castration-resistant prostate cancer and mechanisms of resistance.去势抵抗性前列腺癌中雄激素受体靶向药物及其耐药机制
Clin Pharmacol Ther. 2015 Dec;98(6):582-9. doi: 10.1002/cpt.256. Epub 2015 Oct 1.
4
Abiraterone switches castration-resistant prostate cancer dependency from adrenal androgens towards androgen receptor variants and glucocorticoid receptor signalling.阿比特龙将去势抵抗性前列腺癌的依赖性从肾上腺雄激素转向雄激素受体变体和糖皮质激素受体信号。
Prostate. 2022 Apr;82(5):505-516. doi: 10.1002/pros.24297. Epub 2022 Jan 17.
5
Understanding the mechanisms of androgen deprivation resistance in prostate cancer at the molecular level.在分子水平上理解前列腺癌雄激素剥夺抗性的机制。
Eur Urol. 2015 Mar;67(3):470-9. doi: 10.1016/j.eururo.2014.09.049. Epub 2014 Oct 8.
6
Lin28 induces resistance to anti-androgens via promotion of AR splice variant generation.Lin28通过促进雄激素受体（AR）剪接变体的产生诱导抗雄激素耐药。
Prostate. 2016 Apr;76(5):445-55. doi: 10.1002/pros.23134. Epub 2015 Dec 30.
7
Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis.雄激素受体在去势抵抗性前列腺癌中的作用及新的靶向雄激素轴药物的耐药机制。
Oncogene. 2014 May 29;33(22):2815-25. doi: 10.1038/onc.2013.235. Epub 2013 Jun 10.
8
Androgen receptor splice variants in the era of enzalutamide and abiraterone.恩杂鲁胺和阿比特龙时代的雄激素受体剪接变体
Horm Cancer. 2014 Oct;5(5):265-73. doi: 10.1007/s12672-014-0190-1. Epub 2014 Jul 22.
9
Targeting persistent androgen receptor signaling in castration-resistant prostate cancer.针对去势抵抗性前列腺癌中持续存在的雄激素受体信号传导
Med Oncol. 2016 May;33(5):44. doi: 10.1007/s12032-016-0759-3. Epub 2016 Apr 4.
10
Androgen receptors in hormone-dependent and castration-resistant prostate cancer.雄激素受体在激素依赖性和去势抵抗性前列腺癌中的作用。
Pharmacol Ther. 2013 Dec;140(3):223-38. doi: 10.1016/j.pharmthera.2013.07.003. Epub 2013 Jul 13.
引用本文的文献
1
TLK1>Nek1 Axis Promotes Nuclear Retention and Activation of YAP with Implications for Castration-Resistant Prostate Cancer.TLK1>Nek1轴促进YAP的核内滞留和激活，对去势抵抗性前列腺癌具有重要意义。
Cancers (Basel). 2024 Aug 22;16(16):2918. doi: 10.3390/cancers16162918.
2
Hsa_circ_0070440 mediates the prognosis and progress of human prostate cancer.人源环状RNA hsa_circ_0070440介导人类前列腺癌的预后和进展。
Histol Histopathol. 2025 Jan;40(1):113-121. doi: 10.14670/HH-18-765. Epub 2024 May 20.
3
Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.去势抵抗性前列腺癌中的Wnt信号传导与治疗抵抗性
Curr Pharmacol Rep. 2023 Oct;9(5):261-274. doi: 10.1007/s40495-023-00333-z. Epub 2023 Sep 19.
4
Small Mitochondria-Targeting Fluorophore with Multifunctional Therapeutic Activities against Prostate Cancer via the HIF1α/OATPs Pathway.通过 HIF1α/OATPs 通路具有多功能治疗活性的靶向小型化线粒体荧光探针用于治疗前列腺癌。
Mol Pharm. 2023 Dec 4;20(12):6226-6236. doi: 10.1021/acs.molpharmaceut.3c00621. Epub 2023 Nov 13.
5
Obtaining New Candidate Peptides for Biological Anticancer Drugs from Enzymatic Hydrolysis of Human and Bovine Hemoglobin.从人血红蛋白和牛血红蛋白的酶解产物中获得生物抗癌药物的新候选肽。
Int J Mol Sci. 2023 Oct 19;24(20):15383. doi: 10.3390/ijms242015383.
6
Targeting Prostate Cancer, the 'Tousled Way'.靶向前列腺癌，“乱糟糟”的方式。
Int J Mol Sci. 2023 Jul 5;24(13):11100. doi: 10.3390/ijms241311100.
7
α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells.α-山竹黄酮促进前列腺癌细胞中雄激素受体及AR-V7剪接变体的体外和体内降解
Cancers (Basel). 2023 Apr 1;15(7):2118. doi: 10.3390/cancers15072118.
8
Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities.前列腺癌中的线粒体改变：在发病机制和种族差异中的作用。
Int J Mol Sci. 2023 Feb 24;24(5):4482. doi: 10.3390/ijms24054482.
9
Functionalized Carbon Nanoparticles as Theranostic Agents and Their Future Clinical Utility in Oncology.功能化碳纳米颗粒作为诊疗试剂及其在肿瘤学中的未来临床应用
Bioengineering (Basel). 2023 Jan 12;10(1):108. doi: 10.3390/bioengineering10010108.
10
Overcoming Cancer Drug Resistance Utilizing PROTAC Technology.利用PROTAC技术克服癌症耐药性。
Front Cell Dev Biol. 2022 Apr 25;10:872729. doi: 10.3389/fcell.2022.872729. eCollection 2022.
本文引用的文献
1
Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5.一项III期随机双盲多中心试验，比较奥替诺隆（TAK-700）联合泼尼松与安慰剂联合泼尼松用于在多西他赛治疗期间或之后病情进展的转移性去势抵抗性前列腺癌患者：ELM-PC 5研究
J Clin Oncol. 2015 Mar 1;33(7):723-31. doi: 10.1200/JCO.2014.56.5119. Epub 2015 Jan 26.
2
Androgen receptor splice variants activating the full-length receptor in mediating resistance to androgen-directed therapy.雄激素受体剪接变体在介导对雄激素靶向治疗的耐药性中激活全长受体。
Oncotarget. 2014 Mar 30;5(6):1646-56. doi: 10.18632/oncotarget.1802.
3
Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment.多西他赛和阿比特龙治疗后进展的转移性去势抵抗性前列腺癌患者中恩扎鲁胺（MDV3100）的临床活性和耐受性。
Cancer. 2014 Apr 1;120(7):968-75. doi: 10.1002/cncr.28518. Epub 2013 Dec 30.
4
Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade.糖皮质激素受体通过绕过雄激素受体阻断来赋予抗雄激素药物耐药性。
Cell. 2013 Dec 5;155(6):1309-22. doi: 10.1016/j.cell.2013.11.012.
5
CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents.CYP17 抑制剂——阿比特龙、C17,20 裂解酶抑制剂和多靶点药物。
Nat Rev Urol. 2014 Jan;11(1):32-42. doi: 10.1038/nrurol.2013.274. Epub 2013 Nov 26.
6
Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial.醋酸阿比特龙联合泼尼松对比单独泼尼松用于化疗初治转移性去势抵抗性前列腺癌男性患者：一项随机 3 期临床试验的患者报告结局结果。
Lancet Oncol. 2013 Nov;14(12):1193-9. doi: 10.1016/S1470-2045(13)70424-8. Epub 2013 Sep 25.
7
Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer.ARN-509，一种新型抗雄激素药物，治疗去势抵抗性前列腺癌的 I 期临床研究。
J Clin Oncol. 2013 Oct 1;31(28):3525-30. doi: 10.1200/JCO.2013.50.1684. Epub 2013 Sep 3.
8
A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer.雄激素合成中的功能获得性突变与去势抵抗性前列腺癌。
Cell. 2013 Aug 29;154(5):1074-1084. doi: 10.1016/j.cell.2013.07.029.
9
Alpha emitter radium-223 and survival in metastatic prostate cancer.α 粒子发射体镭-223 与转移性前列腺癌的生存。
N Engl J Med. 2013 Jul 18;369(3):213-23. doi: 10.1056/NEJMoa1213755.
10
Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone.恩杂鲁胺治疗多西他赛和阿比特龙治疗后进展的去势抵抗性前列腺癌患者。
Eur Urol. 2014 Jan;65(1):30-6. doi: 10.1016/j.eururo.2013.06.042. Epub 2013 Jul 2.
Zotero 插件