摘要：磷酸酶及张力蛋白同源基因 （phosphate and tension homology deleted on chromosome ten，PTEN） 作为抑癌基因，具有脂质磷酸酶活性和蛋白磷酸酶活性，通过 PI3K/AKT/mTOR 等信号通路抑制肿瘤细胞增 殖、转化、侵袭、迁移，并促进细胞凋亡，从而对肿瘤发生发展起到负调控作用。大量研究证明PTEN缺失与前 列腺癌 （prostate cancer, PCa） 进展和不良预后密切相关，因此针对恢复 PTEN基因表达及调控相关信号通路 有望成为PTEN相关肿瘤的潜在治疗策略，PTEN状态可能作为PCa预后判断及分层治疗的生物标志物。本文就抑癌基因PTEN在PCa预后判断及治疗中的最新研究进展进行综述，以探讨靶向PTEN的治疗潜能。

暂无相关信息！

[1] SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021,71(3):209-249

[2] 王宁,刘硕,杨雷,等.2018全球癌症统计报告解读[J].肿瘤综合治 疗电子杂志,2019,5(1):87-97

[3] EBNER M, LUCIC I, LEONARD TA, et al. PI(3,4,5) P3 Engagement Restricts Akt Activity to Cellular Membranes [J]. Mol Cell, 2017,65(3):416-431

[4] LEE YR, CHEN M, PANDOLFI PP. The functions and regulation of the PTEN tumour suppressor: new modes and prospects [J]. Nat Rev Mol Cell Biol, 2018,19(9):547- 562

[5] LIU W, LAITINEN S, KHAN S, et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer [J]. Nat Med, 2009,15(5):559-565

[6] JAMASPISHVILI T, BERMAN DM, ROSS AE, et al. Clinical implications of PTEN loss in prostate cancer [J]. Nat Rev Urol, 2018,15(4):222-234

[7] LOTAN TL, HEUMANN A, RICO SD, et al. PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospec-tive prostatectomy cohort [J]. Oncotarget, 2017,8(39): 65566-65576

[8] LOTAN TL, GUREL B, SUTCLIFFE S, et al. PTEN protein loss by immunostaining: analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients [J]. Clin Cancer Res, 2011,17(20): 6563-6573

[9] BRAMHECHA YM, ROUZBEH S, GUERARD KP, et al. The combination of PTEN deletion and 16p13.3 gain in prostate cancer provides additional prognostic information in patients treated with radical prostatectomy [J]. Mod Pathol, 2019,32(1):128-138

[10] JAMASPISHVILI T, PATEL PG, NIU Y, et al. Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN) [J]. J Natl Cancer Inst, 2020,112(11):1098-1104

[11] HAMID AA, GRAY KP, HUANG Y, et al. Loss of PTEN Expression Detected by Fluorescence Immunohistochemistry Predicts Lethal Prostate Cancer in Men Treated with Prostatectomy [J]. Eur Urol Oncol, 2019,2(5):475- 482

[12] YE X, ZHAO L, KANG J. Expression and significance of PTEN and Claudin-3 in prostate cancer [J]. Oncol Lett, 2019,17(6):5628-5634

[13] LIU W, HOU J, PETKEWICZ J, et al. Feasibility and performance of a novel probe panel to detect somatic DNA copy number alterations in clinical specimens for predicting prostate cancer progression [J]. Prostate, 2020,80 (14):1253-1262

[14] LIU W, XIE CC, THOMAS CY, et al. Genetic markers associated with early cancer- specific mortality following prostatectomy [J]. Cancer, 2013,119(13):2405-2412

[15] LAPOINTE J, LI C, GIACOMINI CP, et al. Genomic profiling reveals alternative genetic pathways of prostate tumorigenesis [J]. Cancer Res, 2007,67(18):8504-8510

[16] HANEY NM, FAISAL FA, LU J, et al. PTEN Loss with ERG Negative Status is Associated with Lethal Disease after Radical Prostatectomy [J]. J Urol, 2020,203(2): 344-350

[17] GAN Y, CHEN Q, LEI Y. Regulation of paclitaxel sensitivity in prostate cancer cells by PTEN/maspin signaling [J]. Oncol Lett, 2017,14(4):4977-4982

[18] SEKINO Y, HAN X, KAWAGUCHI T, et al. TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer[J]. Int J Mol Sci, 2019,20(16): 3936

[19] ERDOGAN S, DOGANLAR O, DOGANLAR ZB, et al. Naringin sensitizes human prostate cancer cells to paclitaxel therapy[J]. Prostate Int, 2018,6(4):126-135

[20] SANCHEZ BG, BORT A, MATEOS- GOMEZ PA, et al. Combination of the natural product capsaicin and docetaxel synergistically kills human prostate cancer cells through the metabolic regulator AMP- activated kinase [J]. Cancer Cell Int, 2019,19(1):1-14

[21] HANCOC U, COSULICH S, HANSON L,et al. Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN- deficient breast and prostate tumors alone and in combination with docetaxel [J]. Mol Cancer Ther, 2015,14 (1):48-58

[22] LYNCH JT, POLANSKA UM, HANCOX U, et al. Combined Inhibition of PI3Kbeta and mTOR Inhibits Growth of PTEN- null Tumors [J]. Mol Cancer Ther, 2018,17(11):2309-2319

[23] OWUSU- BRACKETT N, ZHAO M, AKCAKANAT A, et al. Targeting PI3Kbeta alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss [J]. Oncotarget, 2020,11(11):969-981

[24] KOLINSKY MP, RESCIGNO P, BIANCHINI D, et al. A phase Ⅰ dose- escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration- resistant prostate cancer [J]. Ann Oncol, 2020,31(5):619-625

[25] HERBERTS C, MURTHA AJ, FU S, et al. Activating AKT1 and PIK3CA Mutations in Metastatic CastrationResistant Prostate Cancer [J]. Eur Urol, 2020,78(6):834- 844

[26] BONO JS, DE GIORGI U, RODRIGUES DN, et al. Randomized Phase Ⅱ Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss [J]. Clin Cancer Res, 2019,25(3):928-936

[27] KMAK JA, AGARWAL N, HE Y, et al. Exceptional Response to Everolimus in a Patient with Metastatic Castrate-Resistant Prostate Cancer Harboring a PTEN Inactivating Mutation [J]. Case Rep Oncol, 2020,13(1):456-461

[28] LUSZCZAK S, KUMAR C, SATHYADEVAN VK, et al. PIM kinase inhibition: co- targeted therapeutic approaches in prostate cancer [J]. Signal Transduct Target Ther, 2020, 5(1):1-10

[29] YAMAMOTO Y, DE VELASCO MA, KURA Y, et al. Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN- deficient of prostate cancer [J]. J Transl Med, 2015,13(1):1-12

[30] WOZNIAK DJ, HITCHINSON B, GILIC MB, et al. Vemurafenib Inhibits Active PTK6 in PTEN- null Prostate Tumor Cells [J]. Mol Cancer Ther, 2019,18(5):937-946

[31] MA L, YAN Y, BAI Y, et al. Overcoming EZH2 Inhibitor Resistance by Taxane in PTEN- Mutated Cancer [J]. Theranostics, 2019,9(17):5020-5034

[32] ANTONARAKIS ES, PIULATS JM, GROSS- GOUPIL M, et al. Pembrolizumab for Treatment-Refractory Metastatic Castration- Resistant Prostate Cancer: Multicohort,Open- Label Phase Ⅱ KEYNOTE-199 Study [J]. J Clin Oncol, 2020,38(5):395-405

[33] HOLL EK, MCNAMARA MA, HEALY P, et al. Prolonged PSA stabilization and overall survival following sipuleucel- T monotherapy in metastatic castration- resistant prostate cancer patients [J]. Prostate Cancer Prostatic Dis, 2019,22(4):588-592

[34] CONCIATORI F, BAZZICHETTO C, FALCONE I, et al. PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy [J]. Int J Mol Sci, 2020,21(15):5337

[35] VIDOTTO T, SAGGIORO FP, JAMASPISHVILI T, et al. PTEN- deficient prostate cancer is associated with an immunosuppressive tumor microenvironment mediated by increased expression of IDO1 and infiltrating FoxP3 + T regulatory cells[J]. Prostate, 2019,79(9):969-979

[36] PATNAIK A, SWANSON KD, CSIZMADIA E, et al. Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity [J]. Cancer Discov, 2017,7(7):750-765

[37] ALLOTT EH, EBOT EM, STOPSACK KH, et al. Statin Use Is Associated with Lower Risk of PTEN- Null and Lethal Prostate Cancer [J]. Clin Cancer Res, 2020,26 (5):1086-1093

[38] LOVERIDGE CJ, SLATER S, CAMPBELL KJ, et al. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration [J]. Oncogene, 2020,39(8):1797-1806

[39] ZHAO D, CAI L, LU X, et al. Chromatin Regulator CHD1 Remodels the Immunosuppressive Tumor Microenvironment in PTEN- Deficient Prostate Cancer [J]. Cancer Discov, 2020,10(9):1374-1387. 

顾君,陈振杰,何泽喜,等. 磷酸酶及张力蛋白同源基因与前列腺癌的研究进展[J]. 泌尿外科杂志（电子版）,2021,13(3):85-89,93. DOI:10.3969/j.issn.1674-7410.2021.03.021.

暂无相关信息！

前列腺癌 （prostate cancer，PCa） 作为世界上 最常见的男性恶性肿瘤之一，发病率和死亡率始终 居高不下。据最新统计，2020年全球新发 PCa约 141 万余例，发生 PCa相关死亡约 37万余例[1] 。发达国家 发病率高于发展中国家，但我国 PCa 发病率近年来 呈显著增长的趋势，目前已位居我国男性恶性肿瘤 的第 6位[2] ，而且 PCa易发生转移和进展，对人们的 健康和生活产生了极大的威胁，因此，探寻针对 PCa 的治疗靶点和预测标志物迫在眉睫。

人第10号染色体缺失的磷酸酶及张力蛋白同源 基 因 （phosphate and tension homology deleted on chromosome ten, PTEN） 是一个重要的抑癌基 因，其表达水平的降低或缺失在诸多恶性肿瘤发生 发展中起重要作用。多项研究证实 PTEN 通过调控 PI3K/AKT/mTOR、 MAPK、 PAK/p130cas 等 信 号通路，不仅可以抑制 PCa 细胞的增殖、侵袭、转 移以及细胞周期进展，还能抑制肿瘤血管生成、诱 导细胞凋亡，从而起到抑癌作用。目前许多研究发 现 PTEN 在预测 PCa预后方面也具有重要的指导意 义，有望作为判断 PCa 预后的新型生物学指标。随 着对 PTEN 在 PCa中的作用及其机制研究的不断深 入，PTEN 在 PCa 治疗中的价值也备受关注。因 此，本文就 PTEN 在 PCa治疗和预后判断等方面的 临床作用及研究进展进行综述。

1 PTEN 概述

2 PTEN 对 PCa 的预测作用

3 PTEN 在 PCa 治疗中的进展
    3.1 PTEN 缺失与化疗耐药
    3.2 靶向及联合治疗
        3.2.1 PTEN缺失与P13K/AKT/mTOR抑制剂
        3.2.2 PTEN缺失与 BRAF抑制剂
        3.2.3 PTEN 缺失与组蛋白甲基化转移酶 （enhancer of zeste homolog 2, EZH2） 抑制剂
    3.3 PTEN缺失与 PCa免疫治疗

4 总结与展望

4 总结与展望 

综上，PTEN 作为一个重要的抑癌基因，在抑 制肿瘤发生、发展过程中发挥着重要而又复杂的作 用，但临床上相当一部分 PCa患者表现出 PTEN 表 达水平降低或拷贝数缺失，这部分患者预后往往也 更差，这为 PCa 预后评估带来了新的思路和依据。 随着目前针对 PTEN 靶点的药物在 PCa治疗的临床 前及临床试验中取得了理想的效果，PTEN 逐渐成 为 PCa治疗的新靶点。

但目前对于 PTEN 缺失 PCa发生、发展过程中 的具体分子调控机制尚未明确，需进一步研究阐明 其信号调控机制，以便提供更加明确的理论基础。 鉴于 PTEN 调控网络的复杂性，靶向单一途径可能 导致替代途径的上调，目前许多靶向治疗药物以及 联合治疗方案都尚处于基础研究或临床试验阶段， 仍需进一步临床随机试验以确认其临床获益。此 外，基于 PTEN 拷贝数检测能有效评估 PCa患者的 预后情况，这也为 PCa 预后评估和分层治疗开辟了 新途径。随着今后不断的探索，PTEN 将可能作为 PCa 进展的预测指标和新的治疗靶点，为 PCa 患者 带来福音。

暂无相关信息！

暂无相关信息！