Epidermal growth factor receptor-targeted therapies in esophageal squamous carcinoma_West China Medical Journal

Authors：

WANG Tianyun ,  PENG Feng

Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

PENG Feng, Email: pfwork@126.com

Keywords：

Esophageal squamous carcinoma; Targeted therapy; Anti epidermal growth factor receptor monoclonal antibody; Epidermal growth factor receptor-tyrosine kinase inhibitor

DOI：

10.7507/1002-0179.201804019

Video：

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The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.

Citation： WANG Tianyun, PENG Feng. Epidermal growth factor receptor-targeted therapies in esophageal squamous carcinoma. West China Medical Journal, 2018, 33(4): 454-458. doi: 10.7507/1002-0179.201804019 Copy

1.	Pennathur A, Gibson MK, Jobe BA, et al. Oesophageal carcinoma. Lancet, 2013, 381(9864): 400-412.
2.	Bray F, Jemal A, Grey N, et al. Global cancer transitions according to the human development index (2008-2030): a population-based study. Lancet Oncol, 2012, 13(8): 790-801.
3.	岳杰, 于振涛. 转移性食管癌分子靶向治疗的研究进展. 中国肿瘤临床, 2016(4): 170-172.
4.	Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
5.	Polee MB, Eskens FA, van der Burg ME, et al. Phase Ⅱ study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer. Br J Cancer, 2002, 86(5): 669-673.
6.	Roth AD, Fazio N, Stupp R, et al. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase Ⅱ trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol, 2007, 25(22): 3217-3223.
7.	Ling Y, Chen J, Tao M, et al. A pilot study of nimotuzumab combined with cisplatin and 5-FU in patients with advanced esophageal squamous cell carcinoma. J Thorac Dis, 2012, 4(1): 58-62.
8.	Belkhiri A, El-Rifai W. Advances in targeted therapies and new promising targets in esophageal cancer. Oncotarget, 2015, 6(3): 1348-1358.
9.	Fichter CD, Timme S, Braun JA, et al. EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer. Int J Cancer, 2014, 135(7): 1517-1530.
10.	Yang YL, Xu KL, Zhou Y, et al. Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas. Chin Med J (Engl), 2012, 125(3): 450-454.
11.	Wang KL, Wu TT, Choi IS, et al. Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas - association with poor outcome. Cancer, 2007, 109(4): 658-667.
12.	Song Y, Li L, Ou Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature, 2014, 509(7498): 91-95.
13.	Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med, 2008, 359(11): 1116-1127.
14.	Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med, 2006, 354(6): 567-578.
15.	Ayyappan S, Prabhakar D, Sharma N. Epidermal growth factor receptor (EGFR)-targeted therapies in esophagogastric cancer. Anticancer Res, 2013, 33(10): 4139-4155.
16.	Meng X, Wang J, Sun X, et al. Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: a prospective, multicenter phase Ⅱ trail. Radiother Oncol, 2013, 109(2): 275-280.
17.	Tomblyn MB, Goldman BH, Thomas CR Jr, et al. Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-Ⅱ study of the SWOG (S0414). J Thorac Oncol, 2012, 7(5): 906-912.
18.	Lorenzen S, Schuster T, Porschen R, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase Ⅱ study of the arbeitsgemeinschaft internistische onkologie. Ann Oncol, 2009, 20(10): 1667-1673.
19.	Alsina M, Rivera F, Ramos FJ, et al. A phaseⅡstudy evaluating combined neoadjuvant cetuximab and chemotherapy followed by chemoradiotherapy and concomitant cetuximab in locoregional oesophageal cancer patients. Target Oncol, 2018, 13(1): 69-78.
20.	Ruhstaller T, Pless M, Dietrich D, et al. Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase ⅠB/Ⅱ trial (SAKK 75/06). J Clin Oncol, 2011, 29(6): 626-631.
21.	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. Lancet Oncol, 2013, 14(7): 627-637.
22.	Suntharalingam M, Winter K, Ilson D, et al. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: the NRG oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol, 2017, 3(11): 1520-1528.
23.	Janmaat VT, Bruno MJ, Polinder S, et al. Cost-Effectiveness of cetuximab for advanced esophageal squamous cell carcinoma. PLoS One, 2016, 11(4): e0153943.
24.	Ruhstaller T, Thuss-Patience P, Hayoz S, et al. Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase Ⅲ trial (SAKK 75/08). Ann Oncol, 2018. doi: 10.1093/annonc/mdy105.
25.	Ramakrishnan MS, Eswaraiah A, Crombet T, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs, 2010, 1(1): 41-48.
26.	Zhao L, He LR, Xi M, et al. Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3. J Transl Med, 2012, 10: 249.
27.	Zhao L, Li QQ, Zhang R, et al. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumor Biol, 2012, 33(4): 1115-1123.
28.	Lu M, Wang XC, Shen L, et al. Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: a single centre prospective phase Ⅱ trial. Cancer Sci, 2016, 107(4): 486-490.
29.	Han X, Lu N, Pan Y, et al. Nimotuzumab combined with chemotherapy is a promising treatment for locally advanced and metastatic esophageal cancer. Med Sci Monit, 2017, 23: 412-418.
30.	Ramos-Suzarte M, Lorenzo-Luaces P, Gonzalez Lazo N, et al. Treatment of malignant, non-resectable, epithelial origin esophageal tumors with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther, 2012, 13(8): 600-605.
31.	Ma NY, Cai XW, Fu XL, et al. Safety and efficacy of nimotuzumab in combination with radiotherapy for patients with squamous cell carcinoma of the esophagus. Int J Clin Oncol, 2014, 19(2): 297-302.
32.	Saumell Y, Sanchez L, González S, et al. Overall survival of patients with locally advanced or metastatic esophageal squamous cell carcinoma treated with nimotuzumab in the real world. Adv Ther, 2017, 34(12): 2638-2647.
33.	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. Eur J Cancer, 2018, 88: 21-30.
34.	Lai XJ, Gu Q, Zheng X, et al. Combined nimotuzumab with chemoradiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma: a retrospective study. J Cancer Res Ther, 2016, 12(5, S): 89-95.
35.	Wang CY, Deng JY, Cai XW, et al. High EGFR and low p-Akt expression is associated with better outcome after nimotuzumab-containing treatment in esophageal cancer patients: preliminary clinical result and testable hypothesis. Oncotarget, 2015, 6(21): 18674-18682.
36.	Wang C, Fu X, Cai X, et al. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy. Onco Targets Ther, 201, 9: 117-122.
37.	Garrido G, Tikhomirov IA, Rabasa A, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther, 2011, 11(4): 373-382.
38.	Xu Y, Zheng Y, Yu X, et al. Concurrent radiotherapy with gefitinib in elderly patients with esophageal squamous cell carcinoma: preliminary results of a phase Ⅱ study. Oncotarget, 2015, 6(35): 38429-38439.
39.	Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol, 2014, 15(8): 894-904.
40.	Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase Ⅱ study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol, 2006, 24(10): 1612-1619.
41.	Petty RD, Dahle-Smith A, Stevenson DAJ, et al. Gefitinib and EGFR gene copy number aberrations in esophageal cancer. J Clin Oncol, 2017, 35(20): 2279-2287.
42.	Zhai Y, Hui Z, Wang J, et al. Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal squamous cell carcinoma patients: results of a pilot study. Dis Esophagus, 2013, 26(5): 503-509.
43.	张薛榜, 谢聪颖, 李文峰, 等. 厄洛替尼联合放疗治疗老年食管癌的Ⅱ期临床观察. 中华医学杂志, 2012, 92(23):1615-1617.
44.	Iyer R, Chhatrala R, Shefter T, et al. Erlotinib and radiation therapy for elderly patients with esophageal cancer - clinical and correlative results from a prospective multicenter phase 2 trial. Oncology, 2013, 85(1): 53-58.
45.	Li G, Hu W, Wang J, et al. PhaseⅡstudy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. Int J Radiat Oncol Biol Phys, 2010, 78(5): 1407-1412.
46.	Song T, Du D, Zhang X, et al. Comparative study of radiotherapy plus erlotinib versus chemoradiotherapy for elderly patients with esophageal cancer: a propensity score-matched analysis. Dis Esophagus, 2017, 30(9): 1-10.
47.	Huang J, Fan Q, Lu P, et al. Icotinib in patients with pretreated advanced esophageal squamous cell carcinoma with EGFR overexpression or EGFR gene amplification: a single-arm, multicenter phase 2 study. J Thorac Oncol, 2016, 11(6): 910-917.
48.	Fukuoka S, Kojima T, Koga Y, et al. Preclinical efficacy of Sym004, novel anti-EGFR antibody mixture, in esophageal squamous cell carcinoma cell lines. Oncotarget, 2017, 8(7): 11020-11029.
49.	Kikuchi O, Ohashi S, Horibe T, et al. Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma. Sci Rep, 2016, 6: 22452.
50.	Ng HY, Ko JM, Yu VZ, et al. DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma. Int J Cancer, 2016, 138(12): 2940-2951.

1. Pennathur A, Gibson MK, Jobe BA, et al. Oesophageal carcinoma. Lancet, 2013, 381(9864): 400-412.
2. Bray F, Jemal A, Grey N, et al. Global cancer transitions according to the human development index (2008-2030): a population-based study. Lancet Oncol, 2012, 13(8): 790-801.
3. 岳杰, 于振涛. 转移性食管癌分子靶向治疗的研究进展. 中国肿瘤临床, 2016(4): 170-172.
4. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
5. Polee MB, Eskens FA, van der Burg ME, et al. Phase Ⅱ study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer. Br J Cancer, 2002, 86(5): 669-673.
6. Roth AD, Fazio N, Stupp R, et al. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase Ⅱ trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol, 2007, 25(22): 3217-3223.
7. Ling Y, Chen J, Tao M, et al. A pilot study of nimotuzumab combined with cisplatin and 5-FU in patients with advanced esophageal squamous cell carcinoma. J Thorac Dis, 2012, 4(1): 58-62.
8. Belkhiri A, El-Rifai W. Advances in targeted therapies and new promising targets in esophageal cancer. Oncotarget, 2015, 6(3): 1348-1358.
9. Fichter CD, Timme S, Braun JA, et al. EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer. Int J Cancer, 2014, 135(7): 1517-1530.
10. Yang YL, Xu KL, Zhou Y, et al. Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas. Chin Med J (Engl), 2012, 125(3): 450-454.
11. Wang KL, Wu TT, Choi IS, et al. Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas - association with poor outcome. Cancer, 2007, 109(4): 658-667.
12. Song Y, Li L, Ou Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature, 2014, 509(7498): 91-95.
13. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med, 2008, 359(11): 1116-1127.
14. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med, 2006, 354(6): 567-578.
15. Ayyappan S, Prabhakar D, Sharma N. Epidermal growth factor receptor (EGFR)-targeted therapies in esophagogastric cancer. Anticancer Res, 2013, 33(10): 4139-4155.
16. Meng X, Wang J, Sun X, et al. Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: a prospective, multicenter phase Ⅱ trail. Radiother Oncol, 2013, 109(2): 275-280.
17. Tomblyn MB, Goldman BH, Thomas CR Jr, et al. Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-Ⅱ study of the SWOG (S0414). J Thorac Oncol, 2012, 7(5): 906-912.
18. Lorenzen S, Schuster T, Porschen R, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase Ⅱ study of the arbeitsgemeinschaft internistische onkologie. Ann Oncol, 2009, 20(10): 1667-1673.
19. Alsina M, Rivera F, Ramos FJ, et al. A phaseⅡstudy evaluating combined neoadjuvant cetuximab and chemotherapy followed by chemoradiotherapy and concomitant cetuximab in locoregional oesophageal cancer patients. Target Oncol, 2018, 13(1): 69-78.
20. Ruhstaller T, Pless M, Dietrich D, et al. Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase ⅠB/Ⅱ trial (SAKK 75/06). J Clin Oncol, 2011, 29(6): 626-631.
21. 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. Lancet Oncol, 2013, 14(7): 627-637.
22. Suntharalingam M, Winter K, Ilson D, et al. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: the NRG oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol, 2017, 3(11): 1520-1528.
23. Janmaat VT, Bruno MJ, Polinder S, et al. Cost-Effectiveness of cetuximab for advanced esophageal squamous cell carcinoma. PLoS One, 2016, 11(4): e0153943.
24. Ruhstaller T, Thuss-Patience P, Hayoz S, et al. Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase Ⅲ trial (SAKK 75/08). Ann Oncol, 2018. doi: 10.1093/annonc/mdy105.
25. Ramakrishnan MS, Eswaraiah A, Crombet T, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs, 2010, 1(1): 41-48.
26. Zhao L, He LR, Xi M, et al. Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3. J Transl Med, 2012, 10: 249.
27. Zhao L, Li QQ, Zhang R, et al. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumor Biol, 2012, 33(4): 1115-1123.
28. Lu M, Wang XC, Shen L, et al. Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: a single centre prospective phase Ⅱ trial. Cancer Sci, 2016, 107(4): 486-490.
29. Han X, Lu N, Pan Y, et al. Nimotuzumab combined with chemotherapy is a promising treatment for locally advanced and metastatic esophageal cancer. Med Sci Monit, 2017, 23: 412-418.
30. Ramos-Suzarte M, Lorenzo-Luaces P, Gonzalez Lazo N, et al. Treatment of malignant, non-resectable, epithelial origin esophageal tumors with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther, 2012, 13(8): 600-605.
31. Ma NY, Cai XW, Fu XL, et al. Safety and efficacy of nimotuzumab in combination with radiotherapy for patients with squamous cell carcinoma of the esophagus. Int J Clin Oncol, 2014, 19(2): 297-302.
32. Saumell Y, Sanchez L, González S, et al. Overall survival of patients with locally advanced or metastatic esophageal squamous cell carcinoma treated with nimotuzumab in the real world. Adv Ther, 2017, 34(12): 2638-2647.
33. 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. Eur J Cancer, 2018, 88: 21-30.
34. Lai XJ, Gu Q, Zheng X, et al. Combined nimotuzumab with chemoradiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma: a retrospective study. J Cancer Res Ther, 2016, 12(5, S): 89-95.
35. Wang CY, Deng JY, Cai XW, et al. High EGFR and low p-Akt expression is associated with better outcome after nimotuzumab-containing treatment in esophageal cancer patients: preliminary clinical result and testable hypothesis. Oncotarget, 2015, 6(21): 18674-18682.
36. Wang C, Fu X, Cai X, et al. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy. Onco Targets Ther, 201, 9: 117-122.
37. Garrido G, Tikhomirov IA, Rabasa A, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther, 2011, 11(4): 373-382.
38. Xu Y, Zheng Y, Yu X, et al. Concurrent radiotherapy with gefitinib in elderly patients with esophageal squamous cell carcinoma: preliminary results of a phase Ⅱ study. Oncotarget, 2015, 6(35): 38429-38439.
39. Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol, 2014, 15(8): 894-904.
40. Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase Ⅱ study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol, 2006, 24(10): 1612-1619.
41. Petty RD, Dahle-Smith A, Stevenson DAJ, et al. Gefitinib and EGFR gene copy number aberrations in esophageal cancer. J Clin Oncol, 2017, 35(20): 2279-2287.
42. Zhai Y, Hui Z, Wang J, et al. Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal squamous cell carcinoma patients: results of a pilot study. Dis Esophagus, 2013, 26(5): 503-509.
43. 张薛榜, 谢聪颖, 李文峰, 等. 厄洛替尼联合放疗治疗老年食管癌的Ⅱ期临床观察. 中华医学杂志, 2012, 92(23):1615-1617.
44. Iyer R, Chhatrala R, Shefter T, et al. Erlotinib and radiation therapy for elderly patients with esophageal cancer - clinical and correlative results from a prospective multicenter phase 2 trial. Oncology, 2013, 85(1): 53-58.
45. Li G, Hu W, Wang J, et al. PhaseⅡstudy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. Int J Radiat Oncol Biol Phys, 2010, 78(5): 1407-1412.
46. Song T, Du D, Zhang X, et al. Comparative study of radiotherapy plus erlotinib versus chemoradiotherapy for elderly patients with esophageal cancer: a propensity score-matched analysis. Dis Esophagus, 2017, 30(9): 1-10.
47. Huang J, Fan Q, Lu P, et al. Icotinib in patients with pretreated advanced esophageal squamous cell carcinoma with EGFR overexpression or EGFR gene amplification: a single-arm, multicenter phase 2 study. J Thorac Oncol, 2016, 11(6): 910-917.
48. Fukuoka S, Kojima T, Koga Y, et al. Preclinical efficacy of Sym004, novel anti-EGFR antibody mixture, in esophageal squamous cell carcinoma cell lines. Oncotarget, 2017, 8(7): 11020-11029.
49. Kikuchi O, Ohashi S, Horibe T, et al. Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma. Sci Rep, 2016, 6: 22452.
50. Ng HY, Ko JM, Yu VZ, et al. DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma. Int J Cancer, 2016, 138(12): 2940-2951.

West China Medical Journal

Epidermal growth factor receptor-targeted therapies in esophageal squamous carcinoma

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