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山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (1): 30-35.doi: 10.6040/j.issn.1671-7554.0.2018.1423

• • 上一篇    

去势抵抗性前列腺癌精准治疗的研究进展

王海涛   

  1. 天津医科大学第二医院肿瘤科 天津市泌尿外科研究所, 天津 300211
  • 发布日期:2022-09-27
  • 通讯作者: 王海涛. E-mail:peterrock2000@126.com
  • 基金资助:
    国家自然科学基金(81572543);天津市科技计划项目(17ZXMFSY00040)

Development of precision medicine in the treatment of castration-resistant prostate cancer

WANG Haitao   

  1. Department of Oncology, Second Hospital of Tianjin Medical University;
    Tianjin Institute of Urology, Tianjin 300211, China
  • Published:2022-09-27

摘要: 近年来,我国前列腺癌的发病率呈逐年上升趋势,且多数患者诊断时已为晚期,虽然雄激素剥夺治疗(ADT)能使多数患者的病情在短时间内得到缓解,但几乎所有的患者最终均发展为去势抵抗性前列腺癌(CRPC)。此类患者预后极差,治疗极为棘手,急需探索新的治疗策略。精准医学的出现与癌症基因组高通量测序的兴起使CRPC患者的分子分型成为可能。就前列腺癌的分子分型、临床精准诊治研究进展进行综述,以期探索新的CRPC诊疗之路。

关键词: 去势抵抗性前列腺癌, 精准医学, 高通量测序, 分子靶向治疗

Abstract: The incidence of prostate cancer in China has been increasing in recent years, and most cases have already reached the advanced stage when the diagnosis is confirmed. Although many patients are initially sensitive to androgen deprivation therapy(ADT)and experience temporary tumor regression, nearly all will develop castration-resistant prostate cancer(CRPC), which is difficult to cure and thus has poor prognosis. New therapies for CRPC remains an urgent need. The emergence of precision medicine and high-throughput sequencing of cancer genomes makes molecular typing of CRPC patients possible. This article reviews the molecular typing of prostate cancer and development of precision medicine in the treatment of CRPC.

Key words: Castration-resistant prostate cancer, Precision medicine, High-throughput sequencing, Molecular targeted therapy

中图分类号: 

  • R737.25
[1] Committee on a framework for developing a new taxonomy of disease, Board on Life Sciences, Division on Earth and Life Studies, et al. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease[M]. Washington, DC: National Academies Press, 2011.
[2] Siegel R, Ma JM, Zou ZH, et al. Cancer statistics, 2014[J]. CA A Cancer J Clin, 2014, 64(1): 9-29.
[3] Logothetis CJ, Gallick GE, Maity SN, et al. Molecular classification of prostate cancer progression: foundation for marker-driven treatment of prostate cancer[J]. Cancer Discov, 2013, 3(8): 849-861.
[4] Dehm SM, Schmidt LJ, Heemers HV, et al. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance[J]. Cancer Res, 2008, 68(13): 5469-5477.
[5] Andersen RJ, Mawji NR, Wang J, et al. Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor[J]. Cancer Cell, 2010, 17(6): 535-546.
[6] Magee JA, Chang LW, Stormo GD, et al. Direct, androgen receptor-mediated regulation of the FKBP5 gene via a distal enhancer element[J]. Endocrinology, 2006, 147(1): 590-598.
[7] Mousses S, Wagner U, Chen Y, et al. Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling[J]. Oncogene, 2001, 20(46): 6718-6723.
[8] 孙李斌. FKBP51调控去势抵抗性前列腺癌形成的分子信号及机制研究[D]. 天津: 天津医科大学, 2016,
[9] Beltran H, Rickman DS, Park K, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets[J]. Cancer Discov, 2011, 1(6): 487-495.
[10] Kumar A, Rajendran V, Sethumadhavan R, et al. AKT kinase pathway: a leading target in cancer research[J]. Scientific World Journal, 2013, 2013: 756134. doi:10.1155/2013/756134.
[11] Carver BS, Tran J, Gopalan A, et al. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate[J]. Nat Genet, 2009, 41(5): 619-624.
[12] Robinson D, Van Allen EM, Wu YM, et al. Integrative clinical genomics of advanced prostate cancer[J]. Cell, 2015, 162(2): 454. doi:10.1016/j.cell.2015.06.053.
[13] Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer[J]. N Engl J Med, 2016, 375(5): 443-453.
[14] Goh CL, Eeles RA. Germline genetic variants associated with prostate cancer and potential relevance to clinical practice[J]. Recent Results Cancer Res, 2014, 202: 9-26. doi:10.1007/978-3-642-45195-9_2.
[15] Castro E, Goh C, Olmos D, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer[J]. J Clin Oncol, 2013, 31(14): 1748-1757.
[16] Boysen G, Barbieri CE, Prandi D, et al. SPOP mutation leads to genomic instability in prostate cancer[J]. Elife, 2015, 4e09207. doi:10.7554/eLife.09207.
[17] Ali M, Chung J, Dewal N, et al. 794PDProspective comprehensive genomic profiling(CGP)of 3, 343 primary and metastatic site prostate tumors[J]. Annals of Oncology, 2018, 29(suppl_8): doi:10.1093/annonc/mdy284.003.
[18] Spratt DE, Zumsteg ZS, Feng FY, et al. Translational and clinical implications of the genetic landscape of prostate cancer[J]. Nat Rev Clin Oncol, 2016, 13(10): 597-610.
[19] Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer[J]. Cell, 2015, 163(4): 1011-1025.
[20] 中国抗癌协会泌尿男生殖系肿瘤专业委员会前列腺癌学组. 中国前列腺癌患者基因检测专家共识(2018年版)[J]. 中国癌症杂志, 2018, 28(8): 627-633. Prostate Cancer Working Group of China Anti-Cancer Association Genitourinary Cancer Committee. Expert consensus on genetic testing in Chinese prostate cancer patients(2018 edition)[J]. China Oncology, 2018, 28(8): 627-633.
[21] Antonarakis ES, Lu CX, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer[J]. N Engl J Med, 2014, 371(11): 1028-1038.
[22] Wang HT, Yao YH, Li BG, et al. Neuroendocrine Prostate Cancer(NEPC)progressing from conventional prostatic adenocarcinoma: factors associated with time to development of NEPC and survival from NEPC diagnosis-a systematic review and pooled analysis[J]. J Clin Oncol, 2014, 32(30): 3383-3390.
[23] Maira SM, Pecchi S, Huang AL, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor[J]. Mol Cancer Ther, 2012, 11(2): 317-328.
[24] Carver BS, Chapinski C, Wongvipat J, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer[J]. Cancer Cell, 2011, 19(5): 575-586.
[25] Mateo J, Sandhu S, Miranda S, et al. Abstract CT322: DNA repair defects and antitumor activity with PARP inhibition: TOPARP, a phase II trial of olaparib in metastatic castration resistant prostate cancer[J]. Cancer Res, 2015, 75(15 Supplement): CT322. doi: 10.1158/1538-7445. am2015-ct322.
[26] Sunkel B, Wu DY, Chen Z, et al. Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence[J]. Nucleic Acids Res, 2017, 45(11): 6993. doi:10.1093/nar/gkx282.
[27] de Bono JS, Hussain M, Thiery-Vuillemin A, et al. PROfound: A randomized Phase III trial evaluating olaparib in patients with metastatic castration-resistant prostate cancer and a deleterious homologous recombination DNA repair aberration[J]. JCO, 2017, 35(15_suppl): TPS5091. doi:10.1200/jco.2017.35.15_suppl.tps5091.
[28] Cheng HH, Pritchard CC, Boyd T, et al. Biallelic inactivation of BRCA2 in platinum-sensitive metastatic castration-resistant prostate cancer[J]. Eur Urol, 2016, 69(6): 992-995.
[29] Rae C, Mairs RJ. Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells[J]. International journal of radiation biology, 2017, 93(2): 194-203.
[30] Petersen C, Mansour WY, Koetter A, et al. PO-0745: Switch to PARP1-dependent endjoining: Olaparib-mediated radiosensitization in prostate cancer cells[J]. Radiotherapy and Oncology, 2015, 115: S369. doi:10.1016/S0167-8140(15)40737-6.
[31] Li J, Wang RX, Kong YF, et al. Targeting plk1 to enhance efficacy of olaparib in castration-resistant prostate cancer[J]. Mol Cancer Ther, 2017, 16(3): 469-479.
[32] Zhang W, Liu B, Wu W, et al. Targeting the MYCN-PARP-DNA damage response pathway in neuroendocrine prostate cancer[J]. Clinical Cancer Research, 2018, 24(3): 696-707.
[32] Zhang W, Liu B, Wu WH, et al. Targeting the MYCN-PARP-DNA damage response pathway in neuroendocrine prostate cancer[J]. Clin Cancer Res, 2018, 24(3): 696-707.
[33] Clarke N, Wiechno P, Alekseev B, et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet Oncol, 2018, 19(7): 975-986.
[34] Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy(CA184-043): a multicentre, randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2014, 15(7): 700-712.
[35] Graff JN, Alumkal JJ, Drake CG, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer[J]. Oncotarget, 2016, 7(33): 52810-52817.
[36] Pai-Scherf L, Blumenthal GM, Li H, et al. FDA approval summary: pembrolizumab for treatment of metastatic non-small cell lung cancer: first-line therapy and beyond[J]. Oncologist, 2017, 21(11):1392-1399.
[37] Wu YM, Cieslik M, Lonigro RJ, et al. Inactivation of CDK12 delineates a distinct immunogenic class of advanced prostate cancer[J]. Cell, 2018, 173(7): 1770-1782.
[38] Karzai F, Madan RA, Owens H, et al. A phase 2 study of olaparib and durvalumab in metastatic castrate-resistant prostate cancer(mCRPC)in an unselected population[J]. JCO, 2018, 36(6_suppl): 163. doi:10.1200/jco.2018.36.6_suppl.163.
[39] Wang HT, Zhang J, Wei SQ. Histological and molecular phenotype changes of castration-resistant prostate cancer and acquired resistance to hormonal therapy[C]. Chiago: ASCO, 2015, e16006.
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