安罗替尼联合治疗在肿瘤治疗中的研究进展

doi:10.6040/j.issn.1673-3770.0.2021.374

摘要/Abstract

摘要： 安罗替尼是一种多靶点酪氨酸激酶抑制剂,可以通过调节肿瘤内血管的生成或改变免疫抑制微环境,发挥其抗肿瘤作用。安罗替尼已批准应用于非小细胞肺癌、软组织肉瘤、小细胞肺癌等多种类型肿瘤的临床治疗,并且在部分晚期或复发的患者取得一定治疗效果。多项临床研究发现安罗替尼与化疗、放疗、免疫检查点抑制剂等联合治疗可以显著抑制肿瘤,其治疗效果明显优于安罗替尼单药应用。论文对安罗替尼的作用机制及其在肿瘤中的联合治疗研究进展进行综述。

关键词: 安罗替尼, 联合用药, 肿瘤治疗, 抗血管生成, 免疫微环境

Abstract: Anlotinib is a multi-targeting tyrosine kinase inhibitor that can play an anti-tumor role by regulating angiogenesis in cancer or an immunosuppressive microenvironment. Anlotinib shows therapeutic effects in patients with advanced or recurrent cancer and has been approved for the clinical treatment of non-small cell lung cancer, soft tissue sarcoma, small cell lung cancer, medullary thyroid cancer, and other types of tumors. Clinical studies have found that anlotinib combined with chemotherapy, radiotherapy, and immune-checkpoint inhibitors could inhibit tumor growth and showed significantly better therapeutic effects than anlotinib monotherapy. In this article, we review the mechanism of action of anlotinib and the progress in research on anlotinib in combination with other cancer treatments.

Key words: Anlotinib, Combination medication, Cancer treatment, Antiangiogenesis, Immune microenvironment

中图分类号:

宋晴宋西成. 安罗替尼联合治疗在肿瘤治疗中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 106-112.

SONG QingOverview,SONG XichengGuidance. Research progress of anlotinib combination therapy in cancer treatment[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 106-112.

参考文献

[1] Shen GS, Zheng FC, Ren DF, et al. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development[J]. J Hematol Oncol, 2018, 11(1): 120. doi:10.1186/s13045-018-0664-7.
[2] Xie CY, Wan XZ, Quan HT, et al. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor[J]. Cancer Sci, 2018, 109(4): 1207-1219. doi:10.1111/cas.13536.
[3] Tiseo M, Franciosi V, Ardizzoni A. Multi-target inhibitors in non-small cell lung cancer(NSCLC)[J]. Ann Oncol, 2006, 17(Suppl 2): ii55-ii57. doi:10.1093/annonc/mdj924.
[4] Takahashi S. Vascular endothelial growth factor(VEGF), VEGF receptors and their inhibitors for antiangiogenic tumor therapy[J]. Biol Pharm Bull, 2011, 34(12): 1785-1788. doi:10.1248/bpb.34.1785.
[5] Song F, Hu B, Cheng JW, et al. Anlotinib suppresses tumor progression via blocking the VEGFR2/PI3K/AKT cascade in intrahepatic cholangiocarcinoma[J]. Cell Death Dis, 2020, 11(7): 573. doi:10.1038/s41419-020-02749-7.
[6] Tang XL, Zheng Y, Jiao DM, et al. Anlotinib inhibits cell proliferation, migration and invasion via suppression of c-met pathway and activation of ERK1/2 pathway in H446 cells[J]. Anticancer Agents Med Chem, 2021, 21(6): 747-755. doi:10.2174/1871520620666200718235748.
[7] Lin BY, Song XM, Yang DW, et al. Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFRβ and FGFR1[J]. Gene, 2018, 654: 77-86. doi:10.1016/j.gene.2018.02.026.
[8] Yang Q, Ni LC, Imani S, et al. Anlotinib suppresses colorectal cancer proliferation and angiogenesis via inhibition of AKT/ERK signaling cascade[J]. Cancer Manag Res, 2020, 12: 4937-4948. doi:10.2147/CMAR.S252181.
[9] Qin TT, Liu ZJ, Wang J, et al. Anlotinib suppresses lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma through a process potentially involving VEGFR-3 signaling[J]. Cancer Biol Med, 2020, 17(3): 753-767. doi:10.20892/j.issn.2095-3941.2020.0024.
[10] Liang HG, Wang MZ. Prospect of immunotherapy combined with anti-angiogenic agents in patients with advanced non-small cell lung cancer[J]. Cancer Manag Res, 2019, 11: 7707-7719. doi:10.2147/CMAR.S212238.
[11] Liu SC, Qin TT, Liu ZJ, et al. Anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells[J]. Cell Death Dis, 2020, 11(5): 309. doi:10.1038/s41419-020-2511-3.
[12] Shi JZ, Zhang YJ, Wang JZ, et al. Anlotinib combined with chemoradiotherapy exhibits significant therapeutic efficacy in esophageal squamous cell carcinoma[J]. Front Oncol, 2020, 10: 995. doi:10.3389/fonc.2020.00995.
[13] Yang YL, Li L, Jiang ZS, et al. Anlotinib optimizes anti-tumor innate immunity to potentiate the therapeutic effect of PD-1 blockade in lung cancer[J]. Cancer Immunol Immunother, 2020, 69(12): 2523-2532. doi:10.1007/s00262-020-02641-5.
[14] Liu YC, Wu L, Tong RZ, et al. PD-1/PD-L1 inhibitors in cervical cancer[J]. Front Pharmacol, 2019, 10: 65. doi:10.3389/fphar.2019.00065.
[15] Deng ZM, Liao W, Wei W, et al. Anlotinib as a promising inhibitor on tumor growth of oral squamous cell carcinoma through cell apoptosis and mitotic catastrophe[J]. Cancer Cell Int, 2021, 21(1): 37. doi:10.1186/s12935-020-01721-x.
[16] Gao Q, Jiang YQ, Li XJ, et al. Intratumoral injection of anlotinib hydrogel combined with radiotherapy reduces hypoxia in lewis lung carcinoma xenografts: assessment by micro fluorine-18-fluoromisonidazole positron emission tomography/computed tomography hypoxia imaging[J]. Front Oncol, 2021, 11: 628895. doi:10.3389/fonc.2021.628895.
[17] Guo L, Zhang LY, Guan Y, et al. In vitro studies of H520 cell cycle and apoptosis by anlotinib combined with radiotherapy[J]. Thorac Cancer, 2021, 12(5): 593-602. doi:10.1111/1759-7714.13780.
[18] Wang GY, Sun MX, Jiang YF, et al. Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma[J]. Int J Cancer, 2019, 145(4): 979-993. doi:10.1002/ijc.32180.
[19] Zhao D, Xie B, Yang Y, et al. Progress in immunotherapy for small cell lung cancer[J]. World J Clin Oncol, 2020, 11(6): 370-377. doi:10.5306/wjco.v11.i6.370.
[20] 陈曦, 乔明哲. 免疫检查点抑制剂在复发或转移性头颈鳞癌的治疗进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 42-48. doi: 10.6040/j.issn.1673-3770.1.2019.001. CHEN Xi, QIAO Mingzhe. Progress of immune checkpoint inhibitors in the treatment of recurrent or metastatic head and neck squamous cell carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 42-48. doi: 10.6040/j.issn.1673-3770.1.2019.001.
[21] Li T, Qian YX, Zhang CF, et al. Anlotinib combined with gefitinib can significantly improve the proliferation of epidermal growth factor receptor-mutant advanced non-small cell lung cancer in vitro and in vivo[J]. Transl Lung Cancer Res, 2021, 10(4): 1873-1888. doi:10.21037/tlcr-21-192.
[22] Liu JY, Fan ZF, Li S, et al. Target therapy for metastatic alveolar soft part sarcoma: a retrospective study with 47 cases[J]. Ann Transl Med, 2020, 8(22): 1493. doi:10.21037/atm-20-6377.
[23] Long ZY, Lu YJ, Li MH, et al. Effective treatment of anlotinib in giant delayed pulmonary metastasis of osteosarcoma: a case report and literature review[J]. Ann Palliat Med, 2021, 10(6): 7073-7082. doi:10.21037/apm-20-1790.
[24] Han BH, Li K, Wang QM, et al. Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the ALTER 0303 phase 3 randomized clinical trial[J]. JAMA Oncol, 2018, 4(11): 1569-1575. doi:10.1001/jamaoncol.2018.3039.
[25] Zhou AP, Bai YX, Song Y, et al. Anlotinib versus sunitinib as first-line treatment for metastatic renal cell carcinoma: a randomized phase II clinical trial[J]. Oncologist, 2019, 24(8): e702-e708. doi:10.1634/theoncologist.2018-0839.
[26] He ZL, Liu J, Ma YW, et al. Anlotinib combined with cranial radiotherapy for non-small cell lung cancer patients with brain metastasis: a retrospectively, control study[J]. Cancer Manag Res, 2021, 13: 6101-6111. doi:10.2147/CMAR.S319650.
[27] Zhu X, Tao H, Kong C, et al. 1386P Anlotinib combined with whole brain radiation therapy(WBRT)for advanced non-small cell lung cancer with multiple brain metastases: an open-label, single-arm phase II trial[J]. Ann Oncol, 2020, 31: S881. doi:10.1016/j.annonc.2020.08.1700.
[28] Kong C, Zhu X, Jiang M, et al. Anlotinib in combination with whole brain radiotherapy for advanced non-small-cell lung cancer with brain metastases progressive or developed after at least one lines of prior treatment[J]. Int J Radiat Oncol, 2021, 111(3): e569. doi:10.1016/j.ijrobp.2021.07.1537.
[29] Chai PW, Zhou CD, Jia RB, et al. Orbital involvement by NUT midline carcinoma: new presentation and encouraging outcome managed by radiotherapy combined with tyrosine kinase inhibitor: a case report[J]. Diagn Pathol, 2020, 15(1): 2. doi:10.1186/s13000-019-0922-1.
[30] Jang HS, Woo SR, Song KH, et al. API5 induces cisplatin resistance through FGFR signaling in human cancer cells[J]. Exp Mol Med, 2017, 49(9): e374. doi:10.1038/emm.2017.130.
[31] Sugimoto K, Miyata Y, Nakayama T, et al. Fibroblast Growth Factor-2 facilitates the growth and chemo-resistance of leukemia cells in the bone marrow by modulating osteoblast functions[J]. Sci Rep, 2016, 6: 30779. doi:10.1038/srep30779.
[32] Gao Y, Liu PF, Shi RH. Anlotinib as a molecular targeted therapy for tumors[J]. Oncol Lett, 2020, 20(2): 1001-1014. doi:10.3892/ol.2020.11685.
[33] Wang HY, Chu JF, Zhang P, et al. Safety and efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in Chinese patients with advanced/metastatic soft tissue sarcoma[J]. Onco Targets Ther, 2020, 13: 1561-1568. doi:10.2147/OTT.S235349.
[34] Ni J, Cheng XZ, Chen J, et al. Anlotinib as exploratory therapy for platinum-resistant ovarian cancer: a retrospective study on efficacy and safety[J]. Onco Targets Ther, 2020, 13: 9857-9863. doi:10.2147/OTT.S268613.
[35] Wang HY, Chu JF, Zhao Y, et al. A trial of the safety and efficacy of chemotherapy plus anlotinib vs chemotherapy alone as second- or third-line salvage treatment for advanced non-small cell lung cancer[J]. Cancer Manag Res, 2020, 12: 3827-3834. doi:10.2147/CMAR.S249678.
[36] Chu TQ, Zhong RB, Zhong H, et al. Phase 1b study of sintilimab plus anlotinib as first-line therapy in patients with advanced NSCLC[J]. J Thorac Oncol, 2021, 16(4): 643-652. doi:10.1016/j.jtho.2020.11.026.
[37] Yang SJ, Zhang WJ, Chen Q, et al. Clinical investigation of the efficacy and safety of anlotinib with immunotherapy in advanced non-small cell lung cancer as third-line therapy: a retrospective study[J]. Cancer Manag Res, 2020, 12: 10333-10340. doi:10.2147/CMAR.S280096.
[38] Chen Y, Yang ZY, Wang YN, et al. Pembrolizumab plus chemotherapy or anlotinib vs. pembrolizumab alone in patients with previously treated EGFR-mutant NSCLC[J]. Front Oncol, 2021, 11: 671228. doi:10.3389/fonc.2021.671228.
[39] Yuan M, Fang JM, Zhu ZZ, et al. The clinical activity and safety of anlotinib combined with anti-PD-1 antibodies in patients with advanced solid tumors[J]. J Clin Oncol, 2020, 38(15_suppl): e15081. doi:10.1200/jco.2020.38.15_suppl.e15081.
[40] Wang YN, Zhang QN, Miao LY, et al. Nivolumab in combination with anlotinib achieved remarkable efficacy in a patient with driver-negative lung squamous cell carcinoma and PS of 4[J]. Ann Palliat Med, 2020, 9(6): 4384-4388. doi:10.21037/apm-20-2096.
[41] Jiang M, Zhang XC. Antiangiogenesis combined with immunotherapy to treat advanced small-cell carcinoma of the esophagus resistant to chemotherapy: according to the guidance of next-generation sequencing[J]. Onco Targets Ther, 2021, 14: 1613-1621. doi:10.2147/OTT.S293733.
[42] She L, Su L, Shen LF, et al. Retrospective study of the safety and efficacy of anlotinib combined with dose-dense temozolomide in patients with recurrent glioblastoma[J]. Front Oncol, 2021, 11: 687564. doi:10.3389/fonc.2021.687564.
[43] Zhai CY, Zhang XL, Ren LL, et al. The efficacy and safety of anlotinib combined with PD-1 antibody for third-line or further-line treatment of patients with advanced non-small-cell lung cancer[J]. Front Oncol, 2020, 10: 619010. doi:10.3389/fonc.2020.619010.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed