食管癌的靶向治疗及免疫治疗

doi:10.3760/cma.j.cn371439-20210520-00043

摘要/Abstract

摘要：

食管癌是一种复杂的消化系统恶性肿瘤,目前针对非手术食管癌患者放化疗的研究已达瓶颈。近年来,随着对肿瘤信号通路相关靶点和免疫治疗的深入研究,肿瘤的治疗手段越来越多元化。目前研究表明,多种基因靶点以及免疫受体与食管癌相关,包括表皮生长因子受体、血管内皮生长因子、人表皮生长因子受体-2、程序性死亡蛋白1/程序性死亡蛋白配体1等,此外肿瘤疫苗和过继性细胞治疗也在研究中,这些因素将有助于实现食管癌的个体化及精准化治疗,提高生存率及局部控制率。

关键词: 食管肿瘤, 分子靶向治疗, 免疫疗法

Abstract:

Esophageal cancer is a complex digestive tract cancer. Currently, the study of radiotherapy and chemotherapy for non-surgical esophageal cancer has reached the bottleneck. In recent years, with the in-depth study of tumor signal pathway related targets and immunotherapy, tumor treatment methods are becoming more and more diversified. At present, research shows that a variety of gene targets and immune receptors are related to esophageal cancer, including epidermal growth factor receptor, vascular endothelial growth factor, human epidermal growth factor receptor 2, programmed death-1/programmed death ligand-1, etc. In addition, tumor vaccine and adoptive cell therapy are also being studied. These factors contribute to the individualized and accurate treatment of esophageal cancer and improve survival rate and local control rate.

Key words: Esophageal neoplasms, Molecular targeted therapy, Immunotherapy

周剑烽, 王铁君. 食管癌的靶向治疗及免疫治疗[J]. 国际肿瘤学杂志, 2022, 49(4): 237-242.

Zhou Jianfeng, Wang Tiejun. Targeted therapy and immunotherapy of esophageal cancer[J]. Journal of International Oncology, 2022, 49(4): 237-242.

参考文献 36

[1]	Yang YM, Hong P, Xu WW, et al. Advances in targeted therapy for esophageal cancer[J]. Signal Transduct Target Ther, 2020, 5(1): 229. DOI: 10.038/s41392-020-00323-3. doi: 10.038/s41392-020-00323-3
[2]	He S, Xu J, Liu X, et al. Advances and challenges in the treatment of esophageal cancer[J]. Acta Pharm Sin B, 2021, 11(11): 3379-3392. DOI: 10.1016/j.apsb.2021.03.008. doi: 10.1016/j.apsb.2021.03.008
[3]	Rades D, Bartscht T, Hunold P, et al. Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2)[J]. Strahlenther Onkol, 2020, 196(9): 795-804. DOI: 10.1007/s00066-020-01646-4. doi: 10.1007/s00066-020-01646-4 pmid: 32533228
[4]	Pinto C, Di Fabio F, Siena S, et al. Phase Ⅱ study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study)[J]. Ann Oncol, 2007, 18(3): 510-517. DOI: 10.1093/annonc/mdl459. doi: 10.1093/annonc/mdl459 pmid: 17164226
[5]	Crosby T, Hurt CN, Falk S, et al. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial[J]. Lancet Oncol, 2013, 14(7): 627-637. DOI: 10.1016/S1470-2045(13)70136-0. doi: 10.1016/S1470-2045(13)70136-0
[6]	de Castro Junior G, Segalla JG, de Azevedo SJ, et al. A randomised phase Ⅱ study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial[J]. Eur J Cancer, 2018, 88: 21-30. DOI: 10.1016/j.ejca.2017.10.005. doi: 10.1016/j.ejca.2017.10.005
[7]	Kato K, Ura T, Koizumi W, et al. Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: a phase Ⅰ study[J]. Cancer Sci, 2018, 109(3): 785-793. DOI: 10.1111/cas.13481. doi: 10.1111/cas.13481
[8]	Jing W, Yan W, Liu Y, et al. Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma[J]. Cancer Biol Ther, 2019, 20(8): 1121-1126. DOI: 10.1080/15384047.2019.1598760. doi: 10.1080/15384047.2019.1598760
[9]	Quintero Aldana G, Salgado M, Candamio S, et al. First-line panitumumab plus docetaxel and cisplatin in advanced gastric and gastro-oesophageal junction adenocarcinoma: results of a phase Ⅱ trial[J]. Clin Transl Oncol, 2020, 22(4): 495-502. DOI: 10.1007/s12094-019-02151-6. doi: 10.1007/s12094-019-02151-6 pmid: 31280434
[10]	Yoon H, Karapetyan L, Choudhary A, et al. Phase Ⅱ study of irinotecan plus panitumumab as second-line therapy for patients with advanced esophageal adenocarcinoma[J]. Oncologist, 2018, 23(9): 1004-e102. DOI: 10.1634/theoncologist.2017-0657. doi: 10.1634/theoncologist.2017-0657
[11]	朱勇, 王妮娜, 张云, 等. 盐酸厄洛替尼联合放射治疗对食管癌放射敏感性的影响[J]. 中国肿瘤临床与康复, 2017, 24(9): 1032-1035. DOI: 10.13455/j.cnki.cjcor.2017.09.03. doi: 10.13455/j.cnki.cjcor.2017.09.03
[12]	Wu SX, Wang LH, Luo HL, et al. Randomised phase Ⅲ trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer[J]. Eur J Cancer, 2018, 93: 99-107. DOI: 10.1016/j.ejca.2018.01.085. doi: 10.1016/j.ejca.2018.01.085
[13]	Ku G, Ilson D. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma[J]. Lancet Oncol, 2017, 18(5): e243. DOI: 10.1016/S1470-2045(17)30280-2. doi: 10.1016/S1470-2045(17)30280-2
[14]	Ku GY, Bains MS, Park DJ, et al. Phase Ⅱ study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma[J]. J Gastrointest Oncol, 2016, 7(6): 828-837. DOI: 10.21037/jgo.2016.08.09. doi: 10.21037/jgo.2016.08.09
[15]	Janjigian YY, Vakiani E, Ku GY, et al. Phase Ⅱ trial of sorafenib in patients with chemotherapy refractory metastatic esophageal and gastroesophageal (GE) junction cancer[J]. PLoS One, 2015, 10(8): e0134731. DOI: 10.1371/journal.pone.0134731. doi: 10.1371/journal.pone.0134731
[16]	Wei B, Wang Y, Wang J, et al. Apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer via the Akt/β-catenin pathway[J]. Cancer Cell Int, 2020, 20: 198. DOI: 10.1186/s12935-020-01290-z. doi: 10.1186/s12935-020-01290-z
[17]	Yanwei L, Feng H, Ren P, et al. Safety and efficacy of apatinib monotherapy for unresectable, metastatic esophageal cancer: a single-arm, open-label, phase Ⅱ study[J]. Oncologist, 2020, 25(10): e1464-e1472. DOI: 10.1634/theoncologist.2020-0310. doi: 10.1634/theoncologist.2020-0310
[18]	Liu GF, Chang H, Li BT, et al. Effect of recombinant human endostatin onradiotherapy for esophagus cancer[J]. Asian Pac J Trop Med, 2016, 9(1): 86-90. DOI: 10.1016/j.apjtm.2015.12.017. doi: 10.1016/j.apjtm.2015.12.017
[19]	Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial[J]. Lancet, 2010, 376(9742): 687-697. DOI: 10.1016/S0140-6736(10)61121-X. doi: 10.1016/S0140-6736(10)61121-X
[20]	Zaanan A, Palle J, Soularue E, et al. Trastuzumab in combination with FOLFIRI in patients with advanced HER2-positive gastro-esophageal adenocarcinoma: a retrospective multicenter AGEO study[J]. Target Oncol, 2018, 13(1): 107-112. DOI: 10.1007/s11523-017-0531-4. doi: 10.1007/s11523-017-0531-4 pmid: 29090377
[21]	Makiyama A, Sukawa Y, Kashiwada T, et al. Randomized, phase Ⅱ study of trastuzumab beyond progression in patients with HER2-positive advanced gastric or gastroesophageal junction cancer: WJOG7112G (T-ACT study)[J]. J Clin Oncol, 2020, 38(17): 1919-1927. DOI: 10.1200/JCO.19.03077. doi: 10.1200/JCO.19.03077 pmid: 32208960
[22]	Tehfe M, Tabchi S, Laterza MM, et al. Ramucirumab in HER-2-positive gastroesophageal adenocarcinoma: an argument for overcoming trastuzumab resistance[J]. Future Oncol, 2018, 14(3): 223-228. DOI: 10.2217/fon-2017-0434. doi: 10.2217/fon-2017-0434
[23]	McDermott J, Jimeno A. Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer[J]. Drugs Today (Barc), 2015, 51(1): 7-20. DOI: 10.1358/dot.2015.51.1.2250387. doi: 10.1358/dot.2015.51.1.2250387
[24]	Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma[J]. J Clin Oncol, 2018, 36(1): 61-67. DOI: 10.1200/JCO.2017.74.9846. doi: 10.1200/JCO.2017.74.9846
[25]	Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial[J]. JAMA Oncol, 2018, 4(5): e180013. DOI: 10.1001/jamaoncol.2018.0013. doi: 10.1001/jamaoncol.2018.0013
[26]	Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study[J]. JAMA Oncol, 2019, 5(4): 546-550. DOI: 10.1001/jamaoncol.2018.5441. doi: 10.1001/jamaoncol.2018.5441
[27]	Kato K, Shah MA, Enzinger P, et al. KEYNOTE-590: phase Ⅲ study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer[J]. Future Oncol, 2019, 15(10): 1057-1066. DOI: 10.2217/fon-2018-0609. doi: 10.2217/fon-2018-0609 pmid: 30735435
[28]	Zhang B, Wang X, Li Q, et al. Efficacy of irinotecan-based chemotherapy after exposure to an anti-PD-1 antibody in patients with advanced esophageal squamous cell carcinoma[J]. Chin J Cancer Res, 2019, 31(6): 910-917. DOI: 10.21147/j.issn.1000-9604.2019.06.07. doi: 10.21147/j.issn.1000-9604.2019.06.07
[29]	Huang J, Xu B, Mo H, et al. Safety, activity, and biomarkers of SHR-1210, an anti-PD-1 antibody, for patients with advanced esophageal carcinoma[J]. Clin Cancer Res, 2018, 24(6): 1296-1304. DOI: 10.1158/1078-0432.CCR-17-2439. doi: 10.1158/1078-0432.CCR-17-2439 pmid: 29358502
[30]	Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer[J]. J Clin Oncol, 2018, 36(28): 2836-2844. DOI: 10.1200/JCO.2017.76.6212. doi: 10.1200/JCO.2017.76.6212 pmid: 30110194
[31]	Kato K, Satoh T, Muro K, et al. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2)[J]. Gastric Cancer, 2019, 22(2): 344-354. DOI: 10.1007/s10120-018-0899-6. doi: 10.1007/s10120-018-0899-6 pmid: 30506519
[32]	Daiko H, Marafioti T, Fujiwara T, et al. Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients[J]. Cancer Immunol Immunother, 2020, 69(11): 2247-2257. DOI: 10.1007/s00262-020-02619-3. doi: 10.1007/s00262-020-02619-3
[33]	Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer[J]. Science, 2015, 348(6230): 62-68. DOI: 10.1126/science.aaa4967. doi: 10.1126/science.aaa4967 pmid: 25838374
[34]	Kageyama S, Ikeda H, Miyahara Y, et al. Adoptive transfer of MAGE-A4 T-cell receptor gene-transduced lymphocytes in patients with recurrent esophageal cancer[J]. Clin Cancer Res, 2015, 21(10): 2268-2277. DOI: 10.1158/1078-0432.CCR-14-1559. doi: 10.1158/1078-0432.CCR-14-1559
[35]	Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development[J]. Clin Cancer Res, 2008, 14(23): 7624-7634. DOI: 10.1158/1078-0432.CCR-08-1547. doi: 10.1158/1078-0432.CCR-08-1547 pmid: 19047087
[36]	Moentenich V, Gebauer F, Comut E, et al. Claudin 18.2 expression in esophageal adenocarcinoma and its potential impact on future treatment strategies[J]. Oncol Lett, 2020, 19(6): 3665-3670. DOI: 10.3892/ol.2020.11520. doi: 10.3892/ol.2020.11520 pmid: 32391091