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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

CEA-regulated Oncolytic Virus Anticancer Therapy: A Promising Strategy for Rare Solid Tumors

Author(s): Yuqi Yang, Shuhang Wang, Peiwen Ma, Qiyu Tang, Yandong Li, Yuan Fang, Qi Zhu, Wei Tao, Yan Zha* and Ning Li*

Volume 22, Issue 2, 2022

Published on: 10 March, 2022

Page: [126 - 132] Pages: 7

DOI: 10.2174/1568009622666220202143852

Price: $65

Abstract

Background: Rare solid tumors have attracted much more attention due to the great unmet clinical need, limited treatment options, and poor prognosis. As the most thoroughly studied tumor marker, carcinoembryonic antigen (CEA) can not only overexpress in various common solid tumors but also in several rare solid tumors. Oncolytic virus therapy has achieved excellent anticancer effects in the past decades. Due to the specific high expression of CEA in certain tumor tissues but not in normal tissues, CEA has been applied to improve the tumor specificity of gene expression.

Methods: The studies of CEA expression in rare solid tumors and CEA-regulated oncolytic virus therapy were reviewed.

Results: We showed the types of rare solid tumors with the overexpression of CEA. Elevated serum CEA levels can indicate the diagnosis, response of surgery or system therapy, distal metastasis, recurrence, and survival. Due to high tumor specificity, CEA-regulated OA therapy has demonstrated a surprising antitumor effect for common CEA-positive tumors in preclinical trials.

Conclusion: These data suggested that CEA could be a diagnostic and prognostic biomarker for several rare solid tumors. We proposed the hypothesis that CEA-regulated oncolytic virus therapy could be a promising therapeutic strategy for CEA-positive rare solid tumors.

Keywords: Carcinoembryonic antigen, oncolytic virus, rare, solid tumor, therapy, overexpression.

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[1]
Kang, S. Carcinoembryonic antigen, the most accessible test for predicting colorectal cancer prognosis: Exploring alternative roles. Ann. Coloproctol., 2021, 37(3), 129-130.
[http://dx.doi.org/10.3393/ac.2021.00493.0070] [PMID: 34233114]
[2]
Wang, S.; Huang, H.Y.; Wu, D.; Fang, H.; Ying, J.; Bai, Y.; Yu, Y.; Fang, Y.; Jiang, N.; Sun, C.; Yu, A.; Fan, Q.; Xing, S.; Ni, Y.; Zhang, W.; Wu, C.; Ji, X.; Wang, H.; Guo, Y.; Tang, Q.; Wang, Y.; Tang, Y.; Li, N. Platform study of genotyping-guided precision medicine for rare solid tumours: A study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours. BMJ Open, 2021, 11(6), e044543.
[http://dx.doi.org/10.1136/bmjopen-2020-044543] [PMID: 34083331]
[3]
Gold, P.; Freedman, S.O. Specific carcinoembryonic antigens of the human digestive system. J. Exp. Med., 1965, 122(3), 467-81.
[4]
Hensel, J.A.; Khattar, V.; Ashton, R.; Ponnazhagan, S. Recombinant AAV-CEA tumor vaccine in combination with an immune adjuvant breaks tolerance and provides protective immunity. Mol. Ther. Oncolytics, 2018, 12, 41-48.
[http://dx.doi.org/10.1016/j.omto.2018.12.004] [PMID: 30666318]
[5]
Chen, C.H.; Hsieh, M.C.; Lai, C.C.; Yeh, C.Y.; Chen, J.S.; Hsieh, P.S.; Chiang, J.M.; Tsai, W.S.; Tang, R.; Changchien, C.R.; Wang, J.Y. Lead time of carcinoembryonic antigen elevation in the postoperative follow-up of colorectal cancer did not affect the survival rate after recurrence. Int. J. Colorectal Dis., 2010, 25(5), 567-571.
[http://dx.doi.org/10.1007/s00384-010-0889-6] [PMID: 20162425]
[6]
Chiaravalloti, A.; Fiorentini, A.; Palombo, E.; Rinino, D.; Lacanfora, A.; Danieli, R.; Di Russo, C.; Di Biagio, D.; Squillaci, E.; Schillaci, O. Evaluation of recurrent disease in the re-staging of colorectal cancer by 18F-FDG PET/CT: Use of CEA and CA 19-9 in patient selection. Oncol. Lett., 2016, 12(5), 4209-4213.
[http://dx.doi.org/10.3892/ol.2016.5143] [PMID: 27895793]
[7]
Blumenthal, R.D.; Leon, E.; Hansen, H.J.; Goldenberg, D.M. Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC Cancer, 2007, 7, 2.
[http://dx.doi.org/10.1186/1471-2407-7-2] [PMID: 17201906]
[8]
Marshall, J. Carcinoembryonic antigen-based vaccines. Semin. Oncol., 2003, 30(3)(Suppl. 8), 30-36.
[http://dx.doi.org/10.1016/S0093-7754(03)00233-1] [PMID: 12881810]
[9]
Hall, C.; Clarke, L.; Pal, A.; Buchwald, P.; Eglinton, T.; Wakeman, C.; Frizelle, F. A Review of the role of carcinoembryonic antigen in clinical practice. Ann. Coloproctol., 2019, 35(6), 294-305.
[http://dx.doi.org/10.3393/ac.2019.11.13] [PMID: 31937069]
[10]
Pesonen, S.; Kangasniemi, L.; Hemminki, A. Oncolytic adenoviruses for the treatment of human cancer: Focus on translational and clinical data. Mol. Pharm., 2011, 8(1), 12-28.
[http://dx.doi.org/10.1021/mp100219n] [PMID: 21126047]
[11]
Turnbull, S.; West, E.J.; Scott, K.J.; Appleton, E.; Melcher, A.; Ralph, C. Evidence for oncolytic virotherapy: Where have we got to and where are we going? Viruses, 2015, 7(12), 6291-6312.
[http://dx.doi.org/10.3390/v7122938] [PMID: 26633468]
[12]
Zhou, X.; Xie, G.; Wang, S.; Wang, Y.; Zhang, K.; Zheng, S.; Chu, L.; Xiao, L.; Yu, Y.; Zhang, Y.; Liu, X. Potent and specific antitumor effect for colorectal cancer by CEA and Rb double regulated oncolytic adenovirus harboring ST13 gene. PLoS One, 2012, 7(10), e47566.
[http://dx.doi.org/10.1371/journal.pone.0047566] [PMID: 23077639]
[13]
Zhang, R.; Zhang, X.; Ma, B.; Xiao, B.; Huang, F.; Huang, P.; Ying, C.; Liu, T.; Wang, Y. Enhanced antitumor effect of combining TRAIL and MnSOD mediated by CEA-controlled oncolytic adenovirus in lung cancer. Cancer Gene Ther., 2016, 23(6), 168-177.
[http://dx.doi.org/10.1038/cgt.2016.11] [PMID: 27080225]
[14]
Xiao, B.; Ying, C.; Chen, Y.; Huang, F.; Wang, B.; Fang, H.; Guo, W.; Liu, T.; Zhou, X.; Huang, B.; Liu, X.; Wang, Y. Doxorubicin hydrochloride enhanced antitumour effect of CEA-regulated oncolytic virotherapy in live cancer cells and a mouse model. J. Cell. Mol. Med., 2020, 24(22), 13431-13439.
[http://dx.doi.org/10.1111/jcmm.15966] [PMID: 33251723]
[15]
Wells, S.A., Jr; Asa, S.L.; Dralle, H.; Elisei, R.; Evans, D.B.; Gagel, R.F.; Lee, N.; Machens, A.; Moley, J.F.; Pacini, F.; Raue, F.; Frank-Raue, K.; Robinson, B.; Rosenthal, M.S.; Santoro, M.; Schlumberger, M.; Shah, M.; Waguespack, S.G. Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid, 2015, 25(6), 567-610.
[http://dx.doi.org/10.1089/thy.2014.0335] [PMID: 25810047]
[16]
Romero-Lluch, A.R.; Cuenca-Cuenca, J.I.; Guerrero-Vázquez, R.; Martínez-Ortega, A.J.; Tirado-Hospital, J.L.; Borrego-Dorado, I.; Navarro-González, E. Diagnostic utility of PET/CT with 18F-DOPA and 18F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff. Eur. J. Nucl. Med. Mol. Imaging, 2017, 44(12), 2004-2013.
[http://dx.doi.org/10.1007/s00259-017-3759-4] [PMID: 28646462]
[17]
Turkdogan, S.; Forest, V.I.; Hier, M.P.; Tamilia, M.; Florea, A.; Payne, R.J. Carcinoembryonic antigen levels correlated with advanced disease in medullary thyroid cancer. J. Otolaryngol. Head Neck Surg., 2018, 47(1), 55.
[http://dx.doi.org/10.1186/s40463-018-0303-x] [PMID: 30223887]
[18]
Hajje, G.; Borget, I.; Leboulleux, S.; Chougnet, C.; Al Ghuzlan, A.; Mirghani, H.; Caramella, C.; Hartl, D.; Schlumberger, M.; Baudin, E. Early changes in carcinoembryonic antigen but not in calcitonin levels are correlated with the progression-free survival in medullary thyroid carcinoma patients treated with cytotoxic chemotherapy. Eur. J. Endocrinol., 2012, 168(2), 113-118.
[http://dx.doi.org/10.1530/EJE-12-0771] [PMID: 23093698]
[19]
Meijer, J.A.; le Cessie, S.; van den Hout, W.B.; Kievit, J.; Schoones, J.W.; Romijn, J.A.; Smit, J.W. Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: A structured meta-analysis. Clin. Endocrinol. (Oxf.), 2010, 72(4), 534-542.
[http://dx.doi.org/10.1111/j.1365-2265.2009.03666.x] [PMID: 19563448]
[20]
Aparicio, T.; Zaanan, A.; Svrcek, M.; Laurent-Puig, P.; Carrere, N.; Manfredi, S.; Locher, C.; Afchain, P. Small bowel adenocarcinoma: Epidemiology, risk factors, diagnosis and treatment. Dig. Liver Dis., 2014, 46(2), 97-104.
[http://dx.doi.org/10.1016/j.dld.2013.04.013] [PMID: 23796552]
[21]
Bilimoria, K.Y.; Bentrem, D.J.; Wayne, J.D.; Ko, C.Y.; Bennett, C.L.; Talamonti, M.S. Small bowel cancer in the United States: Changes in epidemiology, treatment, and survival over the last 20 years. Ann. Surg., 2009, 249(1), 63-71.
[http://dx.doi.org/10.1097/SLA.0b013e31818e4641] [PMID: 19106677]
[22]
Zaanan, A.; Costes, L.; Gauthier, M.; Malka, D.; Locher, C.; Mitry, E.; Tougeron, D.; Lecomte, T.; Gornet, J.M.; Sobhani, I.; Moulin, V.; Afchain, P.; Taïeb, J.; Bonnetain, F.; Aparicio, T. Chemotherapy of advanced small-bowel adenocarcinoma: A multicenter AGEO study. Ann. Oncol., 2010, 21(9), 1786-1793.
[http://dx.doi.org/10.1093/annonc/mdq038] [PMID: 20223786]
[23]
Wang, Z.; Ding, Z.; Huang, S.; Zhong, S. Experience in clinical diagnosis and treatment of duodenal tumors. Mol. Clin. Oncol., 2016, 5(6), 731-739.
[http://dx.doi.org/10.3892/mco.2016.1061]
[24]
Mao, K.; Jiang, W.; Liu, J.; Wang, J. Incidence of subsequent cholangiocarcinomas after another malignancy: Trends in a population-based study. Medicine (Baltimore), 2015, 94(8), e596.
[http://dx.doi.org/10.1097/MD.0000000000000596] [PMID: 25715268]
[25]
DeOliveira, M.L.; Cunningham, S.C.; Cameron, J.L.; Kamangar, F.; Winter, J.M.; Lillemoe, K.D. Cholangiocarcinoma: Thirty-one-year experience with 564 patients at a single institution. Ann Surg, 2007, 245(5), 755-62.
[http://dx.doi.org/10.1097/01.sla.0000251366.62632.d3]
[26]
Loosen, S.H.; Roderburg, C.; Kauertz, K.L.; Koch, A.; Vucur, M.; Schneider, A.T. CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma. Sci. Rep., 2017, 7(1), 16975.
[http://dx.doi.org/10.1038/s41598-017-17175-7]
[27]
Chen, S.; Chen, Y.; Yang, J.; Yang, W.; Weng, H.; Li, H.; Liu, D. Primary mucoepidermoid carcinoma of the esophagus. J. Thorac. Oncol., 2011, 6(8), 1426-1431.
[http://dx.doi.org/10.1097/JTO.0b013e31821cfb96] [PMID: 21587086]
[28]
Hagiwara, N.; Tajiri, T.; Tajiri, T.; Miyashita, M.; Sasajima, K.; Makino, H.; Matsutani, T.; Tsuchiya, Y.; Takubo, K.; Yamashita, K. Biological behavior of mucoepidermoid carcinoma of the esophagus. J. Nippon Med. Sch., 2003, 70(5), 401-407.
[http://dx.doi.org/10.1272/jnms.70.401] [PMID: 14578940]
[29]
Benedix, F; Reimer, A; Gastinger, I; Mroczkowski, P; Lippert, H; Kube, R. Primary appendiceal carcinoma--epidemiology, surgery and survival: Results of a German multi-center study. Eur J Surg Oncol, 2010, 36(8), 763-71.
[30]
Carmignani, C.P.; Hampton, R.; Sugarbaker, C.E.; Chang, D.; Sugarbaker, P.H. Utility of CEA and CA 19-9 tumor markers in diagnosis and prognostic assessment of mucinous epithelial cancers of the appendix. J. Surg. Oncol., 2004, 87(4), 162-166.
[http://dx.doi.org/10.1002/jso.20107] [PMID: 15334630]
[31]
Jang, J.Y.; Choi, N.; Ko, Y.H.; Chung, M.K.; Son, Y.I.; Baek, C.H.; Baek, K.H.; Jeong, H.S. Treatment outcomes in metastatic and localized high-grade salivary gland cancer: High chance of cure with surgery and post-operative radiation in T1-2 N0 high- grade salivary gland cancer. BMC Cancer, 2018, 18(1), 672.
[http://dx.doi.org/10.1186/s12885-018-4578-0] [PMID: 29925355]
[32]
He, H.; Chen, G.; Zhou, L.; Liu, Y. A joint detection of CEA and CA-50 levels in saliva and serum of patients with tumors in oral region and salivary gland. J. Cancer Res. Clin. Oncol., 2009, 135(10), 1315-1321.
[http://dx.doi.org/10.1007/s00432-009-0572-x] [PMID: 19322585]
[33]
Metze, D.; Luger, T.A. Ultrastructural localization of Carcinoembryonic Antigen (CEA) glycoproteins and Epithelial Membrane Antigen (EMA) in normal and neoplastic sweat glands. J. Cutan. Pathol., 1996, 23(6), 518-29.
[34]
Latteri, S.; Catania, V.E.; Malaguarnera, G.; Peri, A.; Bertino, G.; Frazzetto, G.; Borzì, A.M.; Biondi, A.; Perrotta, R.E.; Malaguarnera, M. Carcinoembryonic antigen serum levels in nonmelanoma skin cancer. Biomedicines, 2018, 6(1), 24.
[http://dx.doi.org/10.3390/biomedicines6010024] [PMID: 29473860]
[35]
Ramezani, M; Mohamadzaheri, E; Khazaei, S; Najafi, F; Vaisi-Raygani, A; Rahbar, M Comparison of EMA, CEA, CD10 and Bcl-2 biomarkers by immunohistochemistry in squamous cell carcinoma and basal cell carcinoma of the skin. Asian Pac J Cancer Prev, 2016, 17(3), 1379-83.
[36]
Schrewe, H.; Thompson, J.; Bona, M.; Hefta, L.J.; Maruya, A.; Hassauer, M.; Shively, J.E.; von Kleist, S.; Zimmermann, W. Cloning of the complete gene for carcinoembryonic antigen: Analysis of its promoter indicates a region conveying cell type-specific expression. Mol. Cell. Biol., 1990, 10(6), 2738-2748.
[http://dx.doi.org/10.1128/mcb.10.6.2738-2748.1990] [PMID: 2342461]
[37]
Hauck, W.; Stanners, C.P. Transcriptional regulation of the carcinoembryonic antigen gene. Identification of regulatory elements and multiple nuclear factors. J. Biol. Chem., 1995, 270(8), 3602-3610.
[http://dx.doi.org/10.1074/jbc.270.8.3602] [PMID: 7876096]
[38]
Richards, C.A.; Austin, E.A.; Huber, B.E. Transcriptional regulatory sequences of carcinoembryonic antigen: Identification and use with cytosine deaminase for tumor-specific gene therapy. Hum. Gene Ther., 1995, 6(7), 881-893.
[http://dx.doi.org/10.1089/hum.1995.6.7-881] [PMID: 7578407]
[39]
Li, Y.; Chen, Y.; Dilley, J.; Arroyo, T.; Ko, D.; Working, P.; Yu, D.C. Carcinoembryonic antigen-producing cell-specific oncolytic adenovirus, OV798, for colorectal cancer therapy. Mol. Cancer Ther., 2003, 2(10), 1003-1009.
[PMID: 14578465]

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