李明秀;许振;石洪堂;刘志强;

• 1:滨州医学院附属医院

摘要(Abstract)：

宫颈癌作为妇科最常见的恶性肿瘤之一,严重威胁女性的健康。宫颈癌的治疗方式除进行有效的手术及辅助放化疗外,靶向治疗和免疫治疗正在成为治疗晚期和复发性宫颈癌的重要手段。此外,由于单一疗法的局限性及副作用,将免疫治疗与靶向治疗或传统放化疗联合的策略得到了肿瘤界广泛的关注。本文介绍了近年来宫颈癌治疗的新进展,主要包括针对人乳头瘤状病毒及刺猬信号通路的靶向治疗、PD-1途径的免疫治疗以及其联合治疗,为宫颈癌的临床研究及治疗策略提供新的治疗方向。

关键词(KeyWords)： 宫颈癌;PD-1;刺猬信号通路;免疫治疗;联合治疗

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 李明秀;许振;石洪堂;刘志强;

DOI: 10.13283/j.cnki.xdfckjz.2020.09.030

参考文献(References)：

• [1] Liontos M,Kyriazoglou A,Dimitriadis I,et al.Systemic therapy in cervical cancer:30 years in review[J].Critical Rev Oncol Hematol,2019,137(1):9-17
• [2] Pan K,Gong J,Huynh K,et al.Current systemic treatment landscape of advanced gynecologic malignancies[J].Targeted Oncol,2019,14(3):269-283
• [3] Jin BY,Campbell TE,Draper LM,et al.Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model[J].JCI Insight,2018,3(8).pii:99488
• [4] Chan DW,Liu VW,Leung LY,et al.Zic2 synergistically enhances Hedgehog signalling through nuclear retention of Gli1 in cervical cancer cells[J].J Pathol,2011,225(4):525-534
• [5] Bai XY,Lin JY,Zhang XC,et al.High expression of truncated GLI3 is associated with poor overall survival in patients with nonsmall cell lung cancer[J].Cancer Biomark,2013,13(1):37-47
• [6] Wen SY,Yu YQ,Cao SJ,et al.miR-506 acts as a tumor suppressor by directly targeting the Hedgehog pathway transcription factor Gli3 in human cervical cancer[J].Oncogene,2014,34(6):717-725
• [7] Huang C,Lu H,Li J,et al.SOX2 regulates radioresistance in cervical cancer via the Hedgehog signaling pathway[J].Gynecol Oncol,2018,151(3):533-541
• [8] Chaudary N,Pintilie M,Hedley D,et al.Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts[J].Br J Cancer,2017,116(1):50-57
• [9] Kurebayashi J,Koike Y,Ohta Y,et al.Anti-cancer stem cell activity of a Hedgehog inhibitor GANT61 in estrogen receptor-positive breast cancer cells[J].Cancer,2017,108(5):918-930
• [10] Pakish JB,Jazaeri AA.Immunotherapy in gynecologic cancers:are we there yet?[J].Curr Treat Options Oncol,2017,18(10):59
• [11] Wu X,Gu Z,Chen Y,et al.Application of PD-1 blockade in cancer immunotherapy[J].Comput Struct Biotechnol J,2019,17:661-674
• [12] Nishimura H,Nose M,Hiai H,et al.Development of Lupus-like Autoimmune Diseases by Disruption of the PD-1 Gene Encoding an ITIM Motif-Carrying Immunoreceptor[J].Immunity,1999,11(2):141-151
• [13] Orbegoso C,Murali K,Banerjee S.The current status of immunotherapy for cervical cancer[J].Rep Pract Oncol Radiother,2018,23(6):580-588
• [14] Cai H,Yan L,Liu N,et al.IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway[J].Biomed Pharmacother,2020,123:109790
• [15] Tomita Y,Fukasawa S,Shinohara N,et al.Nivolumab versus everolimus in advanced renal cell carcinoma:Japanese subgroup analysis from the CheckMate 025 study[J].Jpn J Clin Oncol,2017,47(7):639-646
• [16] Kasamon YL,de Claro RA,Wang Y,et al.FDA approval summary:nivolumab for the treatment of relapsed or progressive classical Hodgkin lymphoma[J].Oncol,2017,22(5):585-591
• [17] Wang Y,Li G.PD-1/PD-L1 blockade in cervical cancer:current studies and perspectives[J].Front Med,2019,13(4):438-450
• [18] Zhen S,Lu J,Liu YH,et al.Synergistic antitumor effect on cervical cancer by rational combination of PD1 blockade and CRISPR-Cas9-mediated HPV knockout[J].Cancer Gene Ther,2019[Epub ahead of print]
• [19] Liu YL,Zamarin D.Combination immune checkpoint blockade strategies to maximize immune response in gynecological cancers[J].Cur Oncol Rep,2018,20:94
• [20] Dyer BA,Zamarin D,Eskandar RN,et al.Role of immunotherapy in the management of locally advanced and recurrent/metastatic cervical cancer[J].J Natl Compr Canc Netw,2019,17(1):91-97
• [21] Lee L,Matulonis U.Immunotherapy and radiation combinatorial trials in gynecologic cancer:A potential synergy?[J].Gyneco Oncol,2019,154(1):236-245
• [22] Twyman-Saint Victor C,Rech AJ,Maity A,et al.Radiation and dual checkpoint blockade activate nonredundant immune mechanisms in cancer[J].Nature,2015,520(7547):373-377
• [23] Antonia SJ,Villegas A,Daniel D,et al.Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC[J].N Engl J Med,2018,379(24):2342-2350
• [24] Sun NY,Chen YL,Wu WY,et al.Blockade of PD-L1 enhances cancer immunotherapy by regulating dendritic cell maturation and macrophage polarization[J].Cancers,2019,11(9):e1400
• [25] Gadducci A,Guerrieri ME.Immune checkpoint inhibitors in gynecological cancers:update of literature and perspectives of clinical research[J].Anticancer Res,2017,37(11):5955-5965
• [26] Lyons TG.Targeted therapies for triple-negative breast cancer[J].Curr Treat Options Oncol,2019,20(11):82
• [27] Yan Y,Kumar AB,Finnes H,et al.Combining immune checkpoint inhibitors with conventional cancer therapy[J].Front Immunol,2018,9:1739
• [28] Chen YL,Chang MC,Cheng WF.Metronomic chemotherapy and immunotherapy in cancer treatment[J].Cancer Lett,2017,400:282-292
• [29] Chen YL,Lin HW,Chien CL,et al.BTLA blockade enhances cancer therapy by inhibiting IL-6/IL-10-induced CD19 high B lymphocytes[J].J Immunother Cancer,2019,7(1):313
• [30] Riley RS,June CH,Langer R,et al.Delivery technologies for cancer immunotherapy[J].Nat Rev Drug Discov,2019,18(3):175-196