Tumor‑penetrating peptide fused EGFR single‑domain antibody enhances radiation responses following EGFR inhibition in gastric cancer Corrigendum in /10.3892/or.2020.7834

Ji,Fuzhi; Sha,Huizi; Meng,Fanyan; Zhu,Anqing; Ding,Naiqing; Zhang,Hang; Xu,Hui; Qian,Hanqing; Yu,Lixia; Liu,Qizhan; Liu,Baorui

doi:10.3892/or.2018.6532

Tumor‑penetrating peptide fused EGFR single‑domain antibody enhances radiation responses following EGFR inhibition in gastric cancer

Corrigendum in: /10.3892/or.2020.7834

Authors:
- Fuzhi Ji
- Huizi Sha
- Fanyan Meng
- Anqing Zhu
- Naiqing Ding
- Hang Zhang
- Hui Xu
- Hanqing Qian
- Lixia Yu
- Qizhan Liu
- Baorui Liu
View Affiliations

Affiliations: The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China, The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, P.R. China, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: June 27, 2018 https://doi.org/10.3892/or.2018.6532
Pages: 1583-1591

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Radiotherapy has been the primary method for the local control of several types of unresectable tumor, including gastric cancer. Patients with gastric cancer frequently express high levels of epidermal growth factor receptor (EGFR), which have been found to increase following radiotherapy treatment. This provides a basis for the combination of antibodies targeting EGFR and radiotherapy. In our previous study, a protein (anti‑EGFR‑iRGD) with bispecific targets and high permeability was constructed, and its effects on inhibiting the proliferation of gastric cancer cells was investigated. In the present study, the capacity of anti‑EGFR‑iRGD to modulate a radiation response was investigated and the specific mechanisms underlying these interactions were evaluated in gastric cancer cell lines and xenografts exhibiting high levels of EGFR. The radioenhancement of anti‑EGFR‑iRGD was associated with inhibited radiation‑induced upregulation of EGFR, inhibited cell proliferation and promotion of cell apoptosis. In addition, anti‑EGFR‑iRGD appeared to permeate more into the tumor tissue following radiation. These findings indicated that the recombinant protein anti‑EGFR‑iRGD was a selective and effective radiosensitizer in EGFR‑overexpressing gastric cancer cells and xenografts. These results further suggested that anti‑EGFR‑iRGD is a potential superior EGFR‑targeted therapy combined with radiotherapy. Overall, the present study suggested that anti‑EGFR‑iRGD may be a promising candidate for preclinical and clinical use.

View Figures

View References

1	Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, Yang YH, Sano T, Yang HK, Zhang X, et al: Management of gastric cancer in Asia: Resource-stratified guidelines. Lancet Oncol. 14:e535–e547. 2013. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Henning GT, Schild SE, Stafford SL, Donohue JH, Burch PA, Haddock MG and Gunderson LL: Results of irradiation or chemoirradiation for primary unresectable, locally recurrent, or grossly incomplete resection of gastric adenocarcinoma. Int J Radiat Oncol Biol Phys. 46:109–118. 2000. View Article : Google Scholar : PubMed/NCBI
4	Jansen EP, Boot H, Verheij M and van de Velde CJ: Optimal locoregional treatment in gastric cancer. J Clin Oncol. 23:4509–4517. 2005. View Article : Google Scholar : PubMed/NCBI
5	Smalley SR, Gunderson L, Tepper J, Martenson JA Jr, Minsky B, Willett C and Rich T: Gastric surgical adjuvant radiotherapy consensus report: Rationale and treatment implementation. Int J Radiat Oncol Biol Phys. 52:283–293. 2002. View Article : Google Scholar : PubMed/NCBI
6	Salomon DS, Brandt R, Ciardiello F and Normanno N: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 19:183–232. 1995. View Article : Google Scholar : PubMed/NCBI
7	Kim MA, Lee HS, Lee HE, Jeon YK, Yang HK and Kim WH: EGFR in gastric carcinomas: Prognostic significance of protein overexpression and high gene copy number. Histopathology. 52:738–746. 2008. View Article : Google Scholar : PubMed/NCBI
8	Herbst RS: Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 59 Suppl 2:S21–S26. 2004. View Article : Google Scholar
9	Baumann M and Krause M: Targeting the epidermal growth factor receptor in radiotherapy: Radiobiological mechanisms, preclinical and clinical results. Radiother Oncol. 72:257–266. 2004. View Article : Google Scholar : PubMed/NCBI
10	Chinnaiyan P, Huang S, Vallabhaneni G, Armstrong E, Varambally S, Tomlins SA, Chinnaiyan AM and Harari PM: Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res. 65:3328–3335. 2005. View Article : Google Scholar : PubMed/NCBI
11	Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, et al: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 354:567–578. 2006. View Article : Google Scholar : PubMed/NCBI
12	Harari P and Huang S: Radiation combined with EGFR signal inhibitors: Head and Neck cancer focus. Semin Radiat Oncol. 16:38–44. 2006. View Article : Google Scholar : PubMed/NCBI
13	Lammering G: Molecular predictor and promising target: Will EGFR now become a star in radiotherapy? Radiother Oncol. 74:89–91. 2005. View Article : Google Scholar : PubMed/NCBI
14	Yewale C, Baradia D, Vhora I, Patil S and Misra A: Epidermal growth factor receptor targeting in cancer: A review of trends and strategies. Biomaterials. 34:8690–8707. 2013. View Article : Google Scholar : PubMed/NCBI
15	Bell A, Wang ZJ, Arbabi-Ghahroudi M, Chang TA, Durocher Y, Trojahn U, Baardsnes J, Jaramillo ML, Li S, Baral TN, et al: Differential tumor-targeting abilities of three single-domain antibody formats. Cancer Lett. 289:81–90. 2010. View Article : Google Scholar : PubMed/NCBI
16	Sha H, Zou Z, Xin K, Bian X, Cai X, Lu W, Chen J, Chen G, Huang L, Blair AM, et al: Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy. J Control Release. 200:188–200. 2015. View Article : Google Scholar : PubMed/NCBI
17	Balkwill FR and Mantovani A: Cancer-related inflammation: Common themes and therapeutic opportunities. Semin Cancer Biol. 22:1–40. 2012. View Article : Google Scholar : PubMed/NCBI
18	Huang SM, Li J, Armstrong EA and Harari PM: Modulation of radiation response and tumor-induced angiogenesis after epidermal growth factor receptor inhibition by ZD1839 (Iressa). Cancer Res. 62:4300–4306. 2002.PubMed/NCBI
19	Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, Mendelsohn J and Fan Z: In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res. 6:701–708. 2000.PubMed/NCBI
20	Bianco C, Tortora G, Bianco R, Caputo R, Veneziani BM, Caputo R, Damiano V, Troiani T, Fontanini G, Raben D, et al: Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). Clin Cancer Res. 8:3250–3258. 2002.PubMed/NCBI
21	Eriksen JG, Steiniche T and Overgaard J; Danish Head and Neck Cancer study group (DAHANCA), : The influence of epidermal growth factor receptor and tumor differentiation on the response to accelerated radiotherapy of squamous cell carcinomas of the head and neck in the randomized DAHANCA 6 and 7 study. Radiother Oncol. 74:93–100. 2005. View Article : Google Scholar : PubMed/NCBI
22	Bentzen SM, Atasoy BM, Daley FM, Dische S, Richman PI, Saunders MI, Trott KR and Wilson GD: Epidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial. J Clin Oncol. 23:5560–5567. 2005. View Article : Google Scholar : PubMed/NCBI
23	Mendelsohn J and Baselga J: Epidermal growth factor receptor targeting in cancer. Semin Oncol. 33:369–385. 2006. View Article : Google Scholar : PubMed/NCBI
24	Schmidt-Ullrich RK, Mikkelsen RB, Dent P, Todd DG, Valerie K, Kavanagh BD, Contessa JN, Rorrer WK and Chen PB: Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene. 15:1191–1197. 1997. View Article : Google Scholar : PubMed/NCBI
25	Sturla LM, Amorino G, Alexander MS, Mikkelsen RB, Valerie K and Schmidt-Ullrichr RK: Requirement of Tyr-992 and Tyr-1173 in phosphorylation of the epidermal growth factor receptor by ionizing radiation and modulation by SHP2. J Biol Chem. 280:14597–14604. 2005. View Article : Google Scholar : PubMed/NCBI
26	Huang SM, Bock JM and Harari PM: Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res. 59:1935–1940. 1999.PubMed/NCBI
27	Marmor MD, Skaria KB and Yarden Y: Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 58:903–913. 2004. View Article : Google Scholar : PubMed/NCBI
28	Ciardiello F and Tortora G: A novel approach in the treatment of cancer: Targeting the epidermal growth factor receptor. Clin Cancer Res. 7:2958–2970. 2001.PubMed/NCBI
29	Gibson MK, Abraham SC, Wu TT, Burtness B, Heitmiller RF, Heath E and Forastiere A: Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy. Clin Cancer Res. 9:6461–6468. 2003.PubMed/NCBI
30	Giralt J, de las Heras M, Cerezo L, Eraso A, Hermosilla E, Velez D, Lujan J, Espin E, Rosello J, Majó J, et al: The expression of epidermal growth factor receptor results in a worse prognosis for patients with rectal cancer treated with preoperative radiotherapy: A multicenter, retrospective analysis. Radiother Oncol. 74:101–108. 2005. View Article : Google Scholar : PubMed/NCBI
31	Chakravarti A, Seiferheld W, Tu X, Wang H, Zhang HZ, Ang KK, Hammond E, Curran W Jr and Mehta M: Immunohistochemically determined total epidermal growth factor receptor levels not of prognostic value in newly diagnosed glioblastoma multiforme: Report from the radiation therapy oncology group. Int J Radiat Oncol Biol Phys. 62:318–327. 2005. View Article : Google Scholar : PubMed/NCBI
32	Chakravarti A, Winter K, Wu CL, Kaufman D, Hammond E, Parliament M, Tester W, Hagan M, Grignon D, Heney N, et al: Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: A report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 62:309–317. 2005. View Article : Google Scholar : PubMed/NCBI
33	Lee CM, Shrieve DC, Zempolich KA, Lee RJ, Hammond E, Handrahan DL and Gaffney DK: Correlation between human epidermal growth factor receptor family (EGFR, HER2, HER3, HER4), phosphorylated Akt (P-Akt), and clinical outcomes after radiation therapy in carcinoma of the cervix. Gynecol Oncol. 99:415–421. 2005. View Article : Google Scholar : PubMed/NCBI
34	Bonner JA, Maihle NJ, Folven BR, Christianson TJ and Spain K: The interaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities. Int J Radiat Oncol Biol Phys. 29:243–247. 1994. View Article : Google Scholar : PubMed/NCBI
35	Kwok TT and Sutherland RM: Enhancement of sensitivity of human squamous carcinoma cells to radiation by epidermal growth factor. J Natl Cancer Inst. 81:1020–1024. 1989. View Article : Google Scholar : PubMed/NCBI
36	Zhu A, Shaeffer J, Leslie S, Kolm P and El-Mahdi AM: Epidermal growth factor receptor: An independent predictor of survival in astrocytic tumors given definitive irradiation. Int J Radiat Oncol Biol Phys. 34:809–815. 1996. View Article : Google Scholar : PubMed/NCBI
37	Nyati MK, Morgan MA, Feng FY and Lawrence TS: Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 6:876–885. 2006. View Article : Google Scholar : PubMed/NCBI
38	Chen DJ and Nirodi CS: The epidermal growth factor receptor: A role in repair of radiation-induced DNA damage. Clin Cancer Res. 13:6555–6560. 2007. View Article : Google Scholar : PubMed/NCBI
39	Harari PM and Huang SM: Epidermal growth factor receptor modulation of radiation response: Preclinical and clinical development. Semin Radiat Oncol. 12 Suppl 2:S21–S26. 2002. View Article : Google Scholar
40	Ahsan A, Hiniker SM, Davis MA, Lawrence TS and Nyati MK: Role of cell cycle in epidermal growth factor receptor Inhibitor-mediated radiosensitization. Cancer Res. 69:5108–5114. 2009. View Article : Google Scholar : PubMed/NCBI
41	Brown JM and Koong AC: High-dose single-fraction radiotherapy: Exploiting a new biology? Int J Radiat Oncol Biol Phys. 71:324–325. 2008. View Article : Google Scholar : PubMed/NCBI
42	Gerszten PC, Mendel E and Yamada Y: Radiotherapy and radiosurgery for metastatic spine disease: What are the options, indications, and outcomes? Spine (Phila Pa 1976). 34 Suppl 22:S78–S92. 2009. View Article : Google Scholar : PubMed/NCBI
43	Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, et al: Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): A randomised, two-by-two factorial phase 3 study. Lancet Oncol. 16:187–199. 2015. View Article : Google Scholar : PubMed/NCBI