乳腺癌靶向及免疫治疗的临床进展

doi:10.19586/j.2095-2341.2024.0165

生物技术进展 ›› 2025, Vol. 15 ›› Issue (2): 234-240.DOI: 10.19586/j.2095-2341.2024.0165

• 进展评述 • 上一篇

乳腺癌靶向及免疫治疗的临床进展

边裕钦(), 董柯然(), 卢俊孜(), 钟恩鸣, 谷婉莹(), 赵靖舒(), 隋宏书()

山东第一医科大学临床与基础医学院组织学与胚胎学系，济南 250117

收稿日期:2024-10-29 接受日期:2025-02-12 出版日期:2025-03-25 发布日期:2025-04-29
通讯作者: 谷婉莹,赵靖舒,隋宏书
作者简介:边裕钦 E-mail: 1664591559@qq.com；
董柯然E-mail: dongkeranaiwan@outlook.com
卢俊孜E-mail: 19819213858@163.com
基金资助:
国家自然科学基金面上项目(81670004);山东第一医科大学大学生创新创业计划训练项目(2024104391066)

Clinical Progress in Targeted Therapy and Immunotherapy in Breast Cancer

Yuqin BIAN(), Keran DONG(), Junzi LU(), Enming ZHONG, Wanying GU(), Jingshu ZHAO(), Hongshu SUI()

Department of Histology and Embryology，College of Clinical and Basci Medicine，Shandong First Medical University，Jinan 250117，China

Received:2024-10-29 Accepted:2025-02-12 Online:2025-03-25 Published:2025-04-29
Contact: Wanying GU,Jingshu ZHAO,Hongshu SUI

摘要/Abstract

摘要：

乳腺癌是全世界女性最常见的恶性肿瘤，其异质性给治疗带来了极大的挑战，而靶向治疗和免疫治疗的进展为乳腺癌的治疗带来了新的希望。靶向治疗通过抑制特定的靶点抑制肿瘤进展。乳腺癌的潜在治疗靶点包括丝氨酸/苏氨酸激酶（serine/threonine kinases，AKT）、周期蛋白依赖性激酶4和6（cyclin-dependent kinases 4 and 6，CDK4/6）、聚腺苷二磷酸核糖聚合酶（polyadenosine diphosphoribose polymerase，PARP）和各种生长因子。免疫治疗的方法包括免疫检查点阻断、疫苗接种以及过继性T细胞治疗。综述总结了乳腺癌靶向治疗和免疫治疗的临床研究进展，以期为乳腺癌相关研究和疾病治疗提供参考。

关键词: 乳腺癌, 靶向治疗, 免疫治疗, 临床试验

Abstract:

Breast cancer is the most common malignant tumor in women all over the world， and its heterogeneity brings great challenges to treatment. The progress of targeted therapy and immunotherapy brings new hope for the treatment of breast cancer. Targeted therapy inhibits tumor progression by inhibiting specific targets. Potential therapeutic targets for breast cancer include serine/threonine kinases （AKT）?， cyclin-dependent kinases 4 and 6 （CDK4/6）?， polyadenosine diphosphoribose polymerase （PARP）， and various growth factors. Methods of immunotherapy include immune checkpoint blocking， vaccination， and adoptive T cell therapy. The review summarized the clinical progress of targeted therapy and immunotherapy for breast cancer， aiming to providing reference for breast cancer related research and disease treatment.

Key words: breast cancer, targeted therapy, immunotherapy, clinical trials

中图分类号:

Q279

边裕钦, 董柯然, 卢俊孜, 钟恩鸣, 谷婉莹, 赵靖舒, 隋宏书. 乳腺癌靶向及免疫治疗的临床进展[J]. 生物技术进展, 2025, 15(2): 234-240.

Yuqin BIAN, Keran DONG, Junzi LU, Enming ZHONG, Wanying GU, Jingshu ZHAO, Hongshu SUI. Clinical Progress in Targeted Therapy and Immunotherapy in Breast Cancer[J]. Current Biotechnology, 2025, 15(2): 234-240.

参考文献 58

1	BODAI B I, TUSO P. Breast cancer survivorship: a comprehensive review of long-term medical issues and lifestyle recommendations[J]. Perm. J., 2015, 19(2): 48-79.
2	苏晓. 乳腺癌的靶向药物治疗[J]. 医学信息, 2019, 32(12):46-49.
	SU X. Targeted drug therapy for breast cancer[J]. Med. Inf., 2019, 32(12): 46-49.
3	TUFAIL M, CUI J, WU C. Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches[J]. Am. J. Cancer Res., 2022, 12(7): 2920-2949.
4	SANTOLLA M F, MAGGIOLINI M. The FGF/FGFR system in breast cancer: oncogenic features and therapeutic perspectives[J/OL]. Cancers, 2020, 12(10): 3029[2025-02-26]. .
5	CHOI J, LEE S Y. Clinical characteristics and treatment of immune-related adverse events of immune checkpoint inhibitors[J/OL]. Immune Netw., 2020, 20(1): e9[2025-02-26]. .
6	RUSIDZÉ M, ADLANMÉRINI M, CHANTALAT E, et al.. Estrogen receptor-α signaling in post-natal mammary development and breast cancers[J]. Cell. Mol. Life Sci., 2021, 78(15): 5681-5705.
7	KAVARTHAPU R, DUFAU M L. Prolactin receptor gene transcriptional control, regulatory modalities relevant to breast cancer resistance and invasiveness[J/OL]. Front. Endocrinol., 2022, 13: 949396[2025-02-26]. .
8	张文颖, 王思情, 张新妍, 等. JAK2/STAT3作为新型抗癌药物靶点的研究进展[J]. 生物技术进展, 2021, 11(1): 33-39.
	ZHANG W Y, WANG S Q, ZHANG X Y, et al.. Research progress of JAK2/STAT3 served as a novel anticancer drug target[J]. Curr. Biotechnol., 2021, 11(1): 33-39.
9	钮嘉辉, 王小伟, 尤启冬. 选择性雌激素受体下调剂研究进展[J]. 药学进展, 2019, 43(4): 282-292.
	NIU J H, WANG X W, YOU Q D. Advances in the development of selective estrogen receptor down-regulators[J]. Prog. Pharm. Sci., 2019, 43(4): 282-292.
10	KAVARTHAPU R, ANBAZHAGAN R, DUFAU M L. Crosstalk between PRLR and EGFR/HER2 signaling pathways in breast cancer[J/OL]. Cancers, 2021, 13(18): 4685[2025-02-26]. .
11	CARVAJAL A, ESPINOZA N, KATO S, et al.. Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75[J]. Breast Cancer Res. Treat., 2005, 94(2): 171-183.
12	ZHU K, WU Y, HE P, et al.. PI3K/AKT/mTOR-targeted therapy for breast cancer[J/OL]. Cells, 2022, 11(16): 2508[2025-02-26]. .
13	GOLDHIRSCH A, WOOD W C, COATES A S, et al.. Strategies for subtypes: dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J]. Ann. Oncol., 2011, 22(8): 1736-1747.
14	KASHYAP D, GARG V K, SANDBERG E N, et al.. Oncogenic and tumor suppressive components of the cell cycle in breast cancer progression and prognosis[J/OL]. Pharmaceutics, 2021, 13(4): 569[2025-02-26]. .
15	ROCCA A, FAROLFI A, BRAVACCINI S, et al.. Palbociclib (PD0332991): targeting the cell cycle machinery in breast cancer[J]. Expert Opin. Pharmacother., 2014, 15(3): 407-420.
16	HU Y, GAO J, WANG M, et al.. Potential prospect of CDK4/6 inhibitors in triple-negative breast cancer[J]. Cancer Manag. Res., 2021, 13: 5223-5237.
17	SHAH M, NUNES M R, STEARNS V. CDK4/6 inhibitors: game changers in the management of hormone receptor-positive advanced breast cancer?[J]. Oncology, 2018, 32(5): 216-222.
18	MARTIN J M, GOLDSTEIN L J. Profile of abemaciclib and its potential in the treatment of breast cancer[J]. Onco. Targets Ther., 2018, 11: 5253-5259.
19	MCCAIN J. First-in-class CDK4/6 inhibitor palbociclib could usher in a new wave of combination therapies for HR+, HER2- breast cancer[J]. P&T, 2015, 40(8): 511-520.
20	DEMICHELE A, CLARK A S, TAN K S, et al.. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb⁺ advanced breast cancer: phase Ⅱ activity, safety, and predictive biomarker assessment[J]. Clin. Cancer Res., 2015, 21(5): 995-1001.
21	FINN R S, CROWN J P, LANG I, et al.. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study[J]. Lancet Oncol., 2015, 16(1): 25-35.
22	MAYER E L, DUECK A C, MARTIN M, et al.. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol., 2021, 22(2): 212-222.
23	张雪媛,孙建国,彭英,等.聚腺苷二磷酸核糖聚合酶抑制剂的抗肿瘤研究近况[J].药学进展,2013,37(5):215-221.
	ZHANG X Y, SUN J G, PENG Y, et al.. Research status of poly (ADP-ribose) polymerase inhibitors in anti-tumor therapy[J]. Prog. Pharm. Sci., 2013, 37(5): 215-221.
24	PATEL P S, ALGOUNEH A, HAKEM R. Exploiting synthetic lethality to target BRCA1/2-deficient tumors: where we stand[J]. Oncogene, 2021, 40(17): 3001-3014.
25	BORNSTEIN E, JIMENO A. Olaparib for the treatment of ovarian cancer[J]. Drugs Today (Barc), 2016, 52(1): 17-28.
26	ROBSON M, AIM S, SENKUS E, et al.. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation[J]. N. Engl. J. Med., 2017, 377(6): 523-533.
27	ALZAHRANI A S. PI3K/Akt/mTOR inhibitors in cancer: at the bench and bedside[J]. Semin. Cancer Biol., 2019, 59: 125-132.
28	NITULESCU G, VAN DE VENTER M, NITULESCU G, et al.. The Akt pathway in oncology therapy and beyond (review)[J/OL]. Int. J. Oncol., 2018, 53(6): 2319-2331.
29	BHATTACHARJEE N, BARMA S, KONWAR N, et al.. Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: an update[J]. Eur. J. Pharmacol., 2016, 791: 8-24.
30	NITULESCU G M, MARGINA D, JUZENAS P, et al.. Akt inhibitors in cancer treatment: the long journey from drug discovery to clinical use (review)[J]. Int. J. Oncol., 2016, 48(3): 869-885.
31	DOI T, TAMURA K, TANABE Y, et al.. Phase 1 pharmacokinetic study of the oral pan-AKT inhibitor MK-2206 in Japanese patients with advanced solid tumors[J]. Cancer Chemother. Pharmacol., 2015, 76(2): 409-416.
32	HUDIS C, SWANTON C, JANJIGIAN Y Y, et al.. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors[J/OL]. Breast Cancer Res., 2013, 15(6): R110[2025-02-26]. .
33	CHIEN A J, TRIPATHY D, ALBAIN K S, et al.. MK-2206 and standard neoadjuvant chemotherapy improves response in patients with human epidermal growth factor receptor 2-positive and/or hormone receptor-negative breast cancers in the I-SPY 2 trial[J]. J. Clin. Oncol., 2020, 38(10): 1059-1069.
34	SAURA C, RODA D, ROSELLÓ S, et al.. A first-in-human phase Ⅰ study of the ATP-competitive AKT inhibitor ipatasertib demonstrates robust and safe targeting of AKT in patients with solid tumors[J]. Cancer Discov., 2017, 7(1): 102-113.
35	SMYTH L M, TAMURA K, OLIVEIRA M, et al.. Capivasertib, an AKT kinase inhibitor, as monotherapy or in combination with fulvestrant in patients with AKT1 (E17K)-mutant, ER-positive metastatic breast cancer[J]. Clin. Cancer Res., 2020, 26(15): 3947-3957.
36	MADU C O, WANG S, MADU C O, et al.. Angiogenesis in breast cancer progression, diagnosis, and treatment[J]. J. Cancer, 2020, 11(15): 4474-4494.
37	SHAH A A, KAMAL M A, AKHTAR S. Tumor angiogenesis and VEGFR-2: mechanism, pathways and current biological therapeutic interventions[J]. Curr. Drug Metab., 2021, 22(1): 50-59.
38	MILLER K, WANG M, GRALOW J, et al.. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N. Engl. J. Med., 2007, 357(26): 2666-2676.
39	DENKERT C, LIEDTKE C, TUTT A, et al.. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies[J]. Lancet, 2017, 389(10087): 2430-2442.
40	薛雯,贾宇,江一帆,等.免疫检查点抑制剂在肿瘤治疗中的研究进展[J].生物技术进展,2019,9(4):341-349.
	XUE W, JIA Y, JIANG Y F, et al.. Progress on immune checkpoint inhibitors in tumor therapy[J]. Curr. Biotechnol., 2019, 9(4): 341-349.
41	SCHÜTZ F, STEFANOVIC S, MAYER L, et al.. PD-1/PD-L1 pathway in breast cancer[J]. Oncol. Res. Treat., 2017, 40(5): 294-297.
42	LI Y, MIAO W, HE D, et al.. Recent progress on immunotherapy for breast cancer: tumor microenvironment, nanotechnology and more[J/OL]. Front. Bioeng. Biotechnol., 2021, 9: 680315[2025-02-26]. .
43	DEBIEN V, DE CALUWÉ A, WANG X, et al.. Immunotherapy in breast cancer: an overview of current strategies and perspectives[J/OL]. NPJ Breast Cancer, 2023, 9(1): 7[2025-02-26]. .
44	MITTENDORF E A, PHILIPS A V, MERIC-BERNSTAM F, et al.. PD-L1 expression in triple-negative breast cancer[J]. Cancer Immunol. Res., 2014, 2(4): 361-370.
45	ISAACS C, NANDA R, CHIEN J, et al.. Abstract GS5-03: evaluation of anti-PD-1 cemiplimab plus anti-LAG-3 REGN3767 in early-stage, high-risk HER2-negative breast cancer: results from the neoadjuvant I-SPY 2 TRIAL[J/OL]. Cancer Res., 2023, 83(): GS5-3-GS5-03[2025-03-04]..
46	SCHMID P, ADAMS S, RUGO H S, et al.. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer[J]. N. Engl. J. Med., 2018, 379(22): 2108-2121.
47	EMENS L A, ADAMS S, BARRIOS C H, et al.. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis[J]. Ann. Oncol., 2021, 32(8): 983-993.
48	DOMCHEK S M, POSTEL-VINAY S, AIM S, et al.. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study[J]. Lancet Oncol., 2020, 21(9): 1155-1164.
49	MCARTHUR H L, DIAB A, PAGE D B, et al.. A pilot study of preoperative single-dose ipilimumab and/or cryoablation in women with early-stage breast cancer with comprehensive immune profiling[J]. Clin. Cancer Res., 2016, 22(23): 5729-5737.
50	LOI S, FRANCIS P A, ZDENKOWSKI N, et al.. Neoadjuvant ipilimumab and nivolumab in combination with paclitaxel following anthracycline-based chemotherapy in patients with treatment resistant early-stage triple-negative breast cancer (TNBC): a single-arm phase 2 trial[J/OL]. J. Clin. Oncol., 2022, 40(): 602[2025-02-26]. .
51	方超,黄卫人.合成生物学在肿瘤疫苗设计中的应用进展[J].合成生物学,2024,5(2):239-253.
	FANG C, HUANG W R. Progress with the application of synthetic biology in designing of cancer vaccines[J]. Synth. Biol. J., 2024, 5(2): 239-253.
52	CLIFTON G T, PEOPLES G E, MITTENDORF E A. The development and use of the E75 (HER2 369-377) peptide vaccine[J]. Future Oncol., 2016, 12(11): 1321-1329.
53	PEOPLES G E, GURNEY J M, HUEMAN M T, et al.. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients[J]. J. Clin. Oncol., 2005, 23(30): 7536-7545.
54	ZHU S Y, YU K D. Breast cancer vaccines: disappointing or promising?[J/OL]. Front. Immunol., 2022, 13: 828386[2025-02-26]. .
55	ASSADIPOUR Y, ZACHARAKIS N, CRYSTAL J S, et al.. Characterization of an immunogenic mutation in a patient with metastatic triple-negative breast cancer[J]. Clin. Cancer Res., 2017, 23(15): 4347-4353.
56	ZACHARAKIS N, CHINNASAMY H, BLACK M, et al.. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer[J]. Nat. Med., 2018, 24(6): 724-730.
57	DEES S, GANESAN R, SINGH S, et al.. Emerging CAR-T cell therapy for the treatment of triple-negative breast cancer[J]. Mol. Cancer Ther., 2020, 19(12): 2409-2421.
58	NASIRI F, KAZEMI M, MIRAREFIN S M J, et al.. CAR-T cell therapy in triple-negative breast cancer: hunting the invisible devil[J/OL]. Front. Immunol., 2022, 13: 1018786[2025-02-26]. .

[1]	布尔兰·叶尔肯别克, 孙莉莉, 安外尔·约麦尔阿卜拉, 郭文佳. 骨膜蛋白在雌激素受体阳性乳腺癌中的作用分析——基于单细胞RNA测序和批量RNA测序数据[J]. 生物技术进展, 2024, 14(6): 1055-1066.
[2]	曾艳, 祝恒成, 杨康. 脱氧核糖核酸酶1在肾细胞癌中的作用及机制研究[J]. 生物技术进展, 2024, 14(3): 486-491.
[3]	赵维坚, 徐弘庭, 肖向茜, 盛望. 肿瘤干细胞中的Hippo信号通路研究进展[J]. 生物技术进展, 2024, 14(2): 211-220.
[4]	孙莉莉, 安外尔·约麦尔阿卜拉, 刘富中, 布尔兰·叶尔肯别克, 迪丽娜尔·叶尔夏提, 郭文佳. 基于肿瘤相关成纤维细胞基因构建乳腺癌预后预测模型及免疫浸润分析[J]. 生物技术进展, 2024, 14(2): 312-322.
[5]	安外尔·约麦尔阿卜拉, 布尔兰·叶尔肯别克, 孙莉莉, 刘富中, 迪丽娜尔·叶尔夏提, 郭文佳. 基于m5C相关基因构建三阴性乳腺癌预后预测模型及药物敏感性分析[J]. 生物技术进展, 2024, 14(1): 149-159.
[6]	张鹏晓, 胡念. 黑色素瘤免疫治疗作用机制研究进展[J]. 生物技术进展, 2023, 13(6): 900-906.
[7]	杜琳琳, 谢飞, 马雪梅. SALL4的促癌功能及治疗意义[J]. 生物技术进展, 2023, 13(5): 704-711.
[8]	仪杨, 赵鹏翔, 刘梦昱, YAO Mawulikplimi Adzavon, 谢飞, 马雪梅. 富氢水和富氢生理盐水生物医学研究进展——临床试验[J]. 生物技术进展, 2022, 12(3): 344-351.
[9]	彭灿灿, 王惠明. 适合免疫治疗的大鼠抗肾小球基底膜肾炎模型的建立[J]. 生物技术进展, 2022, 12(3): 473-478.
[10]	胡鑫, 麻慧慈, 韩明盛, 原晓红, 杨鸣宇, 马艳琴. 三阴性乳腺癌相关miRNA筛选及其靶基因的生物信息学分析[J]. 生物技术进展, 2022, 12(2): 296-304.
[11]	李书翔, 安丽萍, 梁德娟, 王凯旋, 赵建国. 朊病毒病治疗方法的研究进展[J]. 生物技术进展, 2022, 12(2): 229-235.
[12]	王林琳, 孙振亮. 氨基酸转运体在肿瘤代谢中的研究进展[J]. 生物技术进展, 2022, 12(1): 50-56.
[13]	肖金平, 李程, 曹云娣, 孙志坚, 康平, 兰晓梅. RET原癌基因与肿瘤相关性研究的进展现状[J]. 生物技术进展, 2022, 12(1): 57-62.
[14]	张海涛，张宇新. miR-148a通过靶向调节己糖激酶2基因抑制乳腺癌细胞糖酵解和细胞增殖能力[J]. 生物技术进展, 2020, 10(2): 176-184.
[15]	刘梦昱,谢飞,张鑫,赵鹏翔,. 胶质母细胞瘤免疫治疗研究进展[J]. 生物技术进展, 2019, 9(3): 223-230.

乳腺癌靶向及免疫治疗的临床进展

Clinical Progress in Targeted Therapy and Immunotherapy in Breast Cancer

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 58

相关文章 15

编辑推荐

Metrics

本文评价