Oncoselectivity in Oncolytic Viruses against Colorectal Cancer


In humans colorectal cancer (CRC) is a significant cause of morbidity and mortality. New treatment options are urgently needed to supplement existing therapies. Replication-competent oncolytic viruses (RCOVs) for the treatment of cancerous tumors in vivo is a relatively new therapeutic modality with great but largely unrealized potential against CRC. In the context of oncolytic virus safety, oncoselectivity is an important criterion. It is at the conceptual intersection of viral replication strategy and tumor cell biology that RCOVs acquire their oncoselectivity, and thus their safety. Every aspect of tumor molecular biology which distinguishes it from normal, non-neoplastic cells is a potential target for exploitation. In the first section of this review we will provide an explanation of some of the successful and widely used strategies for improving oncoselectivity in wild-type viruses to make them more suitable as RCOVs. In the second section we will describe some of the characteristics of CRC biology which can be exploited to provide oncoselectivity against CRC. Throughout the review examples of successfully-engineered RCOVs which embody the approach or strategy under discussion are noted. By showing what has been done, we hope to highlight what is possible and what remains to be done to generate oncoselective RCOVs for use against CRC in humans.

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Conrad, S. and Essani, K. (2014) Oncoselectivity in Oncolytic Viruses against Colorectal Cancer. Journal of Cancer Therapy, 5, 1153-1174. doi: 10.4236/jct.2014.513118.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Brenner, H., Kloor, M. and Pox, C.P. (2014) Colorectal Cancer. The Lancet, 383, 1490-1502. http://dx.doi.org/10.1016/S0140-6736(13)61649-9
[2] Siegel, R., Desantis, C. and Jemal, A. (2014) Colorectal Cancer Statistics, 2014. CA: A Cancer Journal for Clinicians, 64, 104-117. http://dx.doi.org/10.3322/caac.21220
[3] Taylor, I. (1996) Liver Metastases from Colorectal Cancer: Lessons from Past and Present Clinical Studies. The British Journal of Surgery, 83, 456-460. http://dx.doi.org/10.1002/bjs.1800830406
[4] American Cancer Society (2014) Colorectal Cancer Facts & Figures 2014-2016. American Cancer Society, Atlanta.
[5] Langan, R.C., Mullinax, J.E., Raiji, M.T., Upham, T., Summers, T., Stojadinovic, A. and Avital, I. (2013) Colorectal Cancer Biomarkers and the Potential Role of Cancer Stem Cells. Journal of Cancer, 4, 241-250. http://dx.doi.org/10.7150/jca.5832
[6] DeVita, V.T. and Chu, E. (2008) A History of Cancer Chemotherapy. Cancer Research, 68, 8643-8653. http://dx.doi.org/10.1158/0008-5472.CAN-07-6611
[7] Shawver, L.K., Slamon, D. and Ullrich, A. (2002) Smart Drugs: Tyrosine Kinase Inhibitors in Cancer Therapy. Cancer Cell, 1, 117-123. http://dx.doi.org/10.1016/S1535-6108(02)00039-9
[8] Weiner, L., Surana, R. and Wang, S. (2010) Monoclonal Antibodies: Versatile Platforms for Cancer Immunotherapy. Nature Reviews Immunology, 10, 317-327. http://dx.doi.org/10.1038/nri2744
[9] Cross, D. and Burmester, J.K. (2006) Gene Therapy for Cancer Treatment: Past, Present and Future. Clinical Medicine & Research, 4, 218-227. http://dx.doi.org/10.3121/cmr.4.3.218
[10] Hergt, R., Dutz, S., Müller, R. and Zeisberger, M. (2006) Magnetic Particle Hyperthermia: Nanoparticle Magnetism and Materials Development for Cancer Therapy. Journal of Physics: Condensed Matter, 18, S2919-S2934. http://dx.doi.org/10.1088/0953-8984/18/38/S26
[11] Wang, A., Langer, R. and Farokhzad, O. (2012) Nanoparticle Delivery of Cancer Drugs. Annual Review of Medicine, 63, 185-198. http://dx.doi.org/10.1146/annurev-med-040210-162544
[12] Brown, S., Brown, E. and Walker, I. (2004) The Present and Future Role of Photodynamic Therapy in Cancer Treatment. The Lancet Oncology, 5, 497-508. http://dx.doi.org/10.1016/S1470-2045(04)01529-3
[13] Fischer, K., Gedroyc, W. and Jolesz, F.A. (2010) Focused Ultrasound as a Local Therapy for Liver Cancer. The Cancer Journal, 16, 118-124. http://dx.doi.org/10.1097/PPO.0b013e3181db7c32
[14] Lukianova-Hleb, E.Y., Ren, X., Sawant, R.R., Wu, X., Torchilin, V.P. and Lapotko, D.O. (2014) On-Demand Intracellular Amplification of Chemoradiation with Cancer-Specific Plasmonic Nanobubbles. Nature Medicine, 20, 778-784.
[15] Sinkovics, J.G. and Horvath, J.C. (2008) Natural and Genetically Engineered Viral Agents for Oncolysis and Gene Therapy of Human Cancers. Archivum Immunologiae et Therapiae Experimentalis, 56, 1-59. http://dx.doi.org/10.1007/s00005-008-0047-9
[16] Martuza, R.L., Malick, A., Markert, J.M., Ruffner, K.L. and Coen, D.M. (1991) Experimental Therapy of Human Glioma by Means of a Genetically Engineered Virus Mutant. Science, 252, 854-856.
[17] Garber, K. (2006) China Approves World’s First Oncolytic Virus Therapy for Cancer Treatment. Journal of the National Cancer Institute, 98, 298-300. http://dx.doi.org/10.1093/jnci/djj111
[18] Hirsch, J. (2006) An Anniversary for Cancer Chemotherapy. JAMA, 296, 1518-1520.
[19] Middleton, M. and Margison, G. (2003) Improvement of Chemotherapy Efficacy by Inactivation of a DNA-Repair Pathway. The Lancet Oncology, 4, 37-44.
[20] Leoni, L. Bailey, B., Reifert, J., Bendall, H.H., Zeller, R.W., Corbeil, J., Elliot, G. and Niemeyer, C.C. (2008) Bendamustine (Treanda) Displays a Distinct Pattern of Cytotoxicity and Unique Mechanistic Features Compared with Other Alkylating Agents. Clinical Cancer Research, 14, 309-317.
[21] Lawley, P.D. and Phillips, D.H. (1996) DNA Adducts from Chemotherapeutic Agents. Mutation Research, 355, 13-40. http://dx.doi.org/10.1016/0027-5107(96)00020-6
[22] Kelly, E. and Russell, S.J. (2007) History of Oncolytic Viruses: Genesis to Genetic Engineering. Molecular Therapy, 15, 651-659.
[23] Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674. http://dx.doi.org/10.1016/j.cell.2011.02.013
[24] Wollmann, G., Ozduman, K. and van den Pol, A.N. (2012) Oncolytic Virus Therapy of Glioblastoma Multiforme: Concepts and Candidates. Cancer Journal, 18, 69-81.
[25] Dorer, D. and Nettelbeck, D. (2009) Targeting Cancer by Transcriptional Control in Cancer Gene Therapy and Viral Oncolysis. Advanced Drug Delivery Reviews, 61, 554-571.
[26] Hemminki, O., Diaconu, I., Cerullo, V., Pesonen, S.K., Kanerva, A., Joensuu, T., Kairemo, K., Laasonen, L., Partanen, K., Kangasniemi, L., Lieber, A., Pesonen, S. and Hemminki, A. (2012) Ad3-hTERT-E1A, a Fully Serotype 3 Oncolytic Adenovirus, in Patients with Chemotherapy Refractory Cancer. Molecular Therapy, 20, 1821-1830. http://dx.doi.org/10.1038/mt.2012.115
[27] He, T.-C., Zhou, S., Da Costa, L.T., Yu, J., Kinzler, K.W. and Vogelstein, V. (1998) A Simplified System for Generating Recombinant Adenoviruses. Proceedings of the National Academy of Sciences of the United States of America, 95, 2509-2514. http://dx.doi.org/10.1073/pnas.95.5.2509
[28] Ginsberg, H.S. (1999) The Life and Times of Adenoviruses. Advances in Virus Research, 54, 1-13. http://dx.doi.org/10.1016/S0065-3527(08)60363-2
[29] Katsafanas G.C. and Moss, B. (2007) Colocalization of Transcription and Translation within Cytoplasmic Poxvirus Factories Coordinates Viral Expression and Subjugates Host Functions. Cell Host & Microbe, 2, 221-228. http://dx.doi.org/10.1016/j.chom.2007.08.005
[30] Moss, B. (2012) Poxvirus Cell Entry: How Many Proteins Does It Take? Viruses, 4, 688-707.
[31] Parato, K., Breitbach, C., Le Boeuf, F., Wang, J., Storbeck, C., Ilkow, C., Diallo, J.-S., Falls, T., Burns, J., Garcia, V., Kanji, F., Evgin, L., Hu, K., Paradis, F., Knowles, S., Hwang, T.-H., Vanderhyden, B., Auer, R., Kirn, D. and Bell, J. (2012) The Oncolytic Poxvirus JX-594 Selectively Replicates in and Destroys Cancer Cells Driven by Genetic Pathways Commonly Activated in Cancers. Molecular Therapy, 20, 749-758. http://dx.doi.org/10.1038/mt.2011.276
[32] Traut, T.W. (1994) Physiological Concentrations of Purines and Pyrimidines. Molecular and Cellular Biochemistry, 140, 1-22. http://dx.doi.org/10.1007/BF00928361
[33] Alegre, M.M., Robison, R.A. and O’Neill, K.L. (2012) Thymidine Kinase 1 Upregulation Is an Early Event in Breast Tumor Formation. Journal of Oncology, 2012, Article ID: 575647.
[34] Mastrangelo M.J., Maguire, H.C., Eisenlohr, L.C., Laughlin, C.E., Monken, C.E., McCue, P.A., Kovatich, A.J. and Lattime, E.C. (1999) Intratumoral Recombinant GM-CSF-Encoding Virus as Gene Therapy in Patients with Cutaneous Melanoma. Cancer Gene Therapy, 6, 409-422.
[35] Park, B.H., Hwang, T., Liu, T.C., Sze, D.Y., Kim, J.S., Kwon, H.C., Oh, S.Y., Han, S.Y., Yoon, J.H., Hong, S.H., Moon, A., Speth, K., Park, C., Ahn, Y.J., Daneshmand, M., Rhee, B.G., Pinedo, H. and Bell, J.C. (2008) Use of a Targeted Oncolytic Poxvirus, JX-594, in Patients with Refractory Primary or Metastatic Liver Cancer: A Phase I Trial. The Lancet Oncology, 9, 533-542. http://dx.doi.org/10.1016/S1470-2045(08)70107-4
[36] Marsh, M. and Helenius, A. (2006) Virus Entry: Open Sesame. Cell, 124, 729-740.
[37] Smith, A.E. and Helenius, A. (2004) How Viruses Enter Animal Cells. Science, 304, 237-241. http://dx.doi.org/10.1126/science.1094823
[38] Leja, J., Nilsson, B., Yu, D., Gustafson, E., Akerstrom, G., Oberg, K., Giandomenico, V. and Essand, M. (2010) Double-Detargeted Oncolytic Adenovirus Shows Replication Arrest in Liver Cells and Retains Neuroendocrine Cell Killing Ability. PLoS ONE, 5, e8916.
[39] Kreppel, F. and Kochanek, S. (2008) Modification of Adenovirus Gene Transfer Vectors with Synthetic Polymers: A Scientific Review and Technical Guide. Molecular Therapy, 16, 16-29.
[40] Fisher, K.D. and Seymour, L.W. (2010) HPMA Copolymers for Masking and Retargeting of Therapeutic Viruses. Advanced Drug Delivery Reviews, 62, 240-245.
[41] Green, N.K., Morrison, J., Hale, S., Briggs, S.S., Stevenson, M., Subr, V., Ulbrich, K., Chandler, L., Mautner, V., Seymour, L.W. and Fisher, K.D. (2008) Retargeting Polymer-Coated Adenovirus to the FGF Receptor Allows Productive Infection and Mediates Efficacy in a Peritoneal Model of Human Ovarian Cancer. The Journal of Gene Medicine, 10, 280-289. http://dx.doi.org/10.1002/jgm.1121
[42] Singh, R., Tian, B. and Kostarelos, K. (2008) Artificial Envelopment of Nonenveloped Viruses: Enhancing Adenovirus Tumor Targeting in Vivo. The FASEB Journal, 22, 3389-3402.
[43] Fishburn, C.S. (2008) The Pharmacology of PEGylation: Balancing PD with PK to Generate Novel Therapeutics. The Journal of Pharmaceutical Sciences, 10, 4167-4183.
[44] Kim, P.H., Sohn, J.-H., Choi, J.-W., Jung, Y., Kim, S.W., Haam, S. and Yun, C.-O. (2011) Active Targeting and Safety Profile of PEG-Modified Adenovirus Conjugated with Herceptin. Biomaterials, 32, 2314-2326. http://dx.doi.org/10.1016/j.biomaterials.2010.10.031
[45] Miest, T.S. and Cattaneo, R. (2014) New Viruses for Cancer Therapy: Meeting Clinical Needs. Nature Reviews Microbiology, 12, 23-34. http://dx.doi.org/10.1038/nrmicro3140
[46] Waehler, R., Russell, S.J. and Curiel, D.T. (2007) Engineering Targeted Viral Vectors for Gene Therapy. Nature Reviews Genetics, 8, 573-587. http://dx.doi.org/10.1038/nrg2141
[47] Shayakhmetov, D.M., Li, Z.Y., Ni, S. and Lieber, A. (2004) Analysis of Adenovirus Sequestration in the Liver, Transduction of Hepatic Cells, and Innate Toxicity after Injection of Fiber-Modified Vectors. Journal of Virology, 78, 5368-5381. http://dx.doi.org/10.1128/JVI.78.10.5368-5381.2004
[48] Doronin, K., Shashkova, E.V., May, S.M., Hofherr, S.E. and Barry, M.A. (2009). Chemical Modification with High Molecular Weight Polyethylene Glycol Reduces Transduction of Hepatocytes and Increases Efficacy of Intravenously Delivered Oncolytic Adenovirus. Human Gene Therapy, 20, 975-988. http://dx.doi.org/10.1089/hum.2009.028
[49] Alemany, R., Suzuki, K. and Curiel, D.T. (2000) Blood Clearance Rates of Adenovirus Type 5 in Mice. The Journal of General Virology, 81, 2605-2609.
[50] Küster, K., Koschel, A., Rohwer, N., Fischer, A., Weidenmann, B. and Anders, M. (2010) Downregulation of the Coxsackie and Adenovirus Receptor in Cancer Cells by Hypoxia Depends on HIF-1alpha. Cancer Gene Therapy, 17, 141-146. http://dx.doi.org/10.1038/cgt.2009.49
[51] Kim, M., Zinn, K.R., Barnett, B.G., Sumerel, L.A., Krasnykh, V., Curiel, D.T. and Douglas, J.T. (2002) The Therapeutic Efficacy of Adenoviral Vectors for Cancer Gene Therapy Is Limited by a Low Level of Primary Adenovirus Receptors on Tumour Cells. European Journal of Cancer, 38, 1917-1926.
[52] Cronin, J., Zhang, X.-Y. and Reiser, J. (2005) Altering the Tropism of Lentiviral Vectors through Pseudotyping. Current Gene Therapy, 5, 387-398. http://dx.doi.org/10.2174/1566523054546224
[53] Kolokoltsov, A., Weaver, S. and Davey, R. (2004) Efficient Functional Pseudotyping of Oncoretroviral and Lentiviral Vectors by Venezuelan Equine Encephalitis Virus Envelope Proteins. Journal of Virology, 79, 756-763. http://dx.doi.org/10.1128/JVI.79.2.756-763.2005
[54] Mathis, J., Stoff-Khalili, M. and Curiel, D. (2005) Oncolytic Adenoviruses—Selective Retargeting to Tumor Cells. Oncogene, 24, 7775-7791. http://dx.doi.org/10.1038/sj.onc.1209044
[55] Laquerre, S., Anderson, D.B., Stolz, D.B. and Glorioso, J.C. (1998) Recombinant Herpes Simplex Virus Type 1 Engineered for Targeted Binding to Erythropoietin Receptor-Bearing Cells. Journal of Virology, 72, 9683-9697.
[56] Mizuguchi, H., Kay, M. and Hayakawa, T. (2001) Approaches for Generating Recombinant Adenovirus Vectors. Advanced Drug Delivery Reviews, 52, 165-176. http://dx.doi.org/10.1016/S0169-409X(01)00215-0
[57] Haviv, Y., Blackwell, J., Kanerva, A., Nagi, P., Krasnykh, V., Dmitriev, I., Wang, M., Naito, S., Lei, X., Hemminki, A., Carey, D. and Curiel, D.T. (2002) Adenoviral Gene Therapy for Renal Cancer Requires Retargeting to Alternative Cellular Receptors. Cancer Research, 62, 4273-4281.
[58] Haisma, H.J. and Geerts, L. (2010) Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response. Open Gene Therapy Journal, 3, 9-14. http://dx.doi.org/10.2174/1875037001003020009
[59] Whelan, S.P. and Wertz, G.W. (2002) Transcription and Replication Initiate at Separate Sites on the Vesicular Stomatitis Virus Genome. Proceedings of the National Academy of Sciences of the United States of America, 99, 9178-9183. http://dx.doi.org/10.1073/pnas.152155599
[60] Martinez, I., Rodriguez, L.L., Jimenez, C., Pauszek, S.J. and Wertz, G.W. (2003) Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host. Journal of Virology, 77, 8039-8047. http://dx.doi.org/10.1128/JVI.77.14.8039-8047.2003
[61] Letchworth, G.J., Rodriguez, L.L. and Del Cbarrera, J. (1999) Vesicular Stomatitis. The Veterinary Journal, 157, 239-260. http://dx.doi.org/10.1053/tvjl.1998.0303
[62] Barber, G.N. (2004) Vesicular Stomatitis Virus as an Oncolytic Vector. Viral Immunology, 17, 516-527. http://dx.doi.org/10.1089/vim.2004.17.516
[63] Stojdl, D.F., Lichty, B.D., tenOver, B.R., Paterson, J.M., Power, A.T., Knowles, S., Marius, R., Reynard, J., Poliquin, L., Atkins, H., Brown, E.G., Durbin, R.K., Durbin, J.E., Hiscott, J. and Bell, J.C. (2003) VSV Strains with Defects in Their Ability to Shutdown Innate Immunity Are Potent Systemic Anti-Cancer Agents. Cancer Cell, 4, 263-275. http://dx.doi.org/10.1016/S1535-6108(03)00241-1
[64] Russell, S.J. (2002) RNA Viruses as Virotherapy Agents. Cancer Gene Therapy, 9, 961-966. http://dx.doi.org/10.1038/sj.cgt.7700535
[65] Hastie, E., Cataldi, M., Mariott, I. and Grdzelishvili, V.A. (2013) Understanding and Altering Cell Tropism of Vesicular Stomatitis Virus. Virus Research, 176, 16-32.
[66] Kretzschmar, E., Buonocore, L., Schnell, M.J. and Rose, J.K. (1997) High-Efficiency Incorporation of Functional Influenza Virus Glycoproteins into Recombinant Vesicular Stomatitis Viruses. Journal of Virology, 71, 5982-5989.
[67] Finkelshtein, D., Werman, A., Novick, D., Barak, S. and Rubinstein, M. (2013) LDL Receptor and Its Family Members Serve as the Cellular Receptors for Vesicular Stomatitis Virus. Proceedings of the National Academy of Sciences of the United States of America, 110, 7306-7311.
[68] Muik, A., Werbizki, J.I., Wilflingesder, D., Giroglou, T., Ebert. O., Kraft, A., Dietrich, U., Zimmer, G., Momma, S. and von Laer, D. (2011) Pseudotyping Vesicular Stomatitis Virus with Lymphocytic Choriomeningitis Virus Glycoproteins Enhances Infectivity for Glioma Cells and Minimizes Neurotropism. Journal of Virology, 85, 5679-5684. http://dx.doi.org/10.1128/JVI.02511-10
[69] Ayala-Breton, C., Barber, G.M., Russell, S.J. and Peng, K.W. (2012) Retargeting Vesicular Stomatitis Virus Using Measles Virus Envelope Glycoproteins. Human Gene Therapy, 23, 484-491.
[70] Holliger, P. and Hudson, P.J. (2005) Engineered Antibody Fragments and the Rise of Single Domains. Nature Biotechnology, 23, 1126-1136. http://dx.doi.org/10.1038/nbt1142
[71] Verheije M. and Rottier, P. (2012) Retargeting of Viruses to Generate Oncolytic Agents. Advances in Virology, 2012, Article ID: 798526.
[72] Pereboeva, L., Komarova, S., Roth, J., Ponnazhagan, S. and Curiel, D. (2007) Targeting EGFR with Metabolically Biotinylated Fiber-Mosaic Adenovirus. Gene Therapy, 14, 627-637.
[73] Shen, Y. and Nemunaitis, J. (2006) Herpes Simplex Virus 1 (HSV-1) for Cancer Treatment. Cancer Gene Therapy, 13, 975-992. http://dx.doi.org/10.1038/sj.cgt.7700946
[74] Karaba, A.H., Kopp, S.J. and Longnecker, R. (2011) Herpesvirus Entry Mediator and Nectin-1 Mediate Herpes Simplex Virus 1 Infection of the Murine Cornea. Journal of Virology, 85, 10041-10047. http://dx.doi.org/10.1128/JVI.05445-11
[75] Cuddington, B.P. and Mossman, K.L. (2014) Permissiveness of Human Cancer Cells to Oncolytic Bovine Herpesvirus 1 Is Mediated in Part by KRAS Activity. Journal of Virology, 88, 6885-6895. http://dx.doi.org/10.1128/JVI.00849-14
[76] Campadelli-Fiume, G., Amasio, M., Avitabile, E., Cerretani, A., Forghieri, C., Gianni, T. and Menotti, L. (2007) The Multipartite System That Mediates Entry of Herpes Simplex Virus into the Cell. Reviews in Medical Virology, 17, 313-326. http://dx.doi.org/10.1002/rmv.546
[77] Di Giovine, P., Settembre, E.C., Bhargava, A.K., Luftig, M.A., Lou, H., Cohen, G.H., Eisenberg, R.J., Krummenacher, C. and Carfi, A. (2011) Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1. PLoS Pathogens, 7, e1002277.
[78] Braun, E., Zimmerman, T., Ben Hur, T., Reinhartz, E., Fellig, Y., Panet, A. and Stiener, I. (2006) Neurotropism of Herpes Simplex Virus Type 1 in Brain Organ Cultures. The Journal of General Virology, 87, 2827-2837. http://dx.doi.org/10.1099/vir.0.81850-0
[79] Nakano, K., Asano, R., Tsumoto, K., Kwon, H., Goins, W.F., Kumagai, I., Cohen, J.B. and Glorioso, J.B. (2005) Herpes Simplex Virus Targeting to the EGF Receptor by a gD-Specific Soluble Bridging Molecule. Molecular Therapy, 11, 617-626. http://dx.doi.org/10.1016/j.ymthe.2004.12.012
[80] Heessen, S. and Fornerod, M. (2007) The Inner Nuclear Envelope as a Transcription Factor Resting Place. EMBO Reports, 8, 914-919. http://dx.doi.org/10.1038/sj.embor.7401075
[81] Nettelbeck, D., Jér?me, V. and Müller, R. (2000) Gene Therapy: Designer Promoters for Tumour Targeting. Trends in Genetics, 16, 174-181. http://dx.doi.org/10.1016/S0168-9525(99)01950-2
[82] Wu, L., Johnson, M. and Sato, M. (2003). Transcriptionally Targeted Gene Therapy to Detect and Treat Cancer. Trends in Molecular Medicine, 9, 421-429.
[83] Sadeghi, H. and Hitt, M. (2005) Transcriptionally Targeted Adenovirus Vectors. Current Gene Therapy, 5, 411-427. http://dx.doi.org/10.2174/1566523054546189
[84] Hardcastle, J., Kurozumi, K., Chiocca, E.A. and Kaur, B. (2007) Oncolytic Viruses Driven by Tumor-Specific Promoters. Current Cancer Drug Targets, 7, 181-189.
[85] Rodriguez, R., Schuur, E.R., Lim, H.Y., Henderson, G.A., Simons, J.W. and Henderson, D.R. (1997) Prostate Attenuated Replication Competent Adenovirus (ARCA) CN706: A Selective Cytotoxic for Prostate-Specific Antigen-Positive Prostate Cancer Cells. Cancer Research, 57, 2559-2563.
[86] Vile, R. and Hart, I. (1993) Use of Tissue-Specific Expression of the Herpes Simplex Virus Thymidine Kinase Gene to Inhibit Growth of Established Murine Melanomas Following Direct Intratumoral Injection of DNA. Cancer Research, 53, 3860-3864.
[87] Miyatake, S., Iyer, A., Martuza, R.L. and Rabkin, S.D. (1997) Transcriptional Targeting of Herpes Simplex Virus for Cell-Specific Replication. Journal of Virology, 71, 5124-5132.
[88] Nettelbeck, D., Rivera, A., Balagué, C., Alemany, R. and Curiel, D. (2002) Novel Oncolytic Adenoviruses Targeted to Melanoma: Specific Viral Replication and Cytolysis by Expression of E1A Mutants from the Tyrosinase Enhancer/Promoter. Cancer Research, 62, 4663-4670.
[89] Matsubara, S., Wada, Y., Gardner, T.A., Egawa, M., Park, M.S., Hsieh, C.L., Zhau, H.E., Kao, C., Kamidono, S., Gillenwater, J.Y and Chung, L.W. (2001) A conditional Replication-Competent Adenoviral Vector, Ad-OC-E1a, to Cotarget Prostate Cancer and Bone Stroma in an Experimental Model of Androgen-Independent Prostate Cancer Bone Metastasis. Cancer Research, 61, 6012-6019.
[90] Kambara, H., Okano, H., Chiocca, E. and Saeki, Y. (2005) An Oncolytic HSV-1 Mutant Expressing ICP34.5 under Control of a Nestin Promoter Increases Survival of Animals Even When Symptomatic from a Brain Tumor. Cancer Research, 65, 2832-2839. http://dx.doi.org/10.1158/0008-5472.CAN-04-3227
[91] Kanai, R., Eguchi, K., Takahashi, M., Goldman, S., Okano, H., Kawase, T. and Yazaki, T. (2006) Enhanced Therapeutic Efficacy of Oncolytic Herpes Vector G207 against Human Non-Small Cell Lung Cancer—Expression of an RNA-Binding Protein, Musashi1, as a Marker for the Tailored Gene Therapy. The Journal of Gene Medicine, 8, 1329-1340. http://dx.doi.org/10.1002/jgm.965
[92] Logg, C., Logg, A., Matusik, R., Bochner, B. and N. Kasahara. (2002) Tissue-Specific Transcriptional Targeting of a Replication-Competent Retroviral Vector. Journal of Virology, 76, 12783-12791. http://dx.doi.org/10.1128/JVI.76.24.12783-12791.2002
[93] Rodriguez, R., Schuur, E.R., Lim, H.Y., Henderson, G.A., Simons, J.W. and Henderson, D.R. (1997) Prostate Attenuated Replication Competent Adenovirus (ARCA) CN706: A Selective Cytotoxic for Prostate-Specific Antigen-Positive Prostate Cancer Cells. Cancer Research, 57, 2559-63.
[94] Wei, C., Willis, R.A., Tilton, B.R., Looney, R.J., Lord, E.M., Barth, R.K and Frelinger, J.G. (1997) Tissue-Specific Expression of the Human Prostate-Specific Antigen Gene in Transgenic Mice: Implications for Tolerance and Immunotherapy. Proceedings of the National Academy of Sciences of the United States of America, 94, 6369-6374. http://dx.doi.org/10.1073/pnas.94.12.6369
[95] Small, E.J., Carducci, M.A., Burke, J.M., Rodriguez, R., Fong, L., van Ummersen, L., Yu, D.C., Aimi, J., Ando, D., Working, P., Kirn, D and Wilding, G. (2006) A Phase I Trial of Intravenous CG7870, a Replication-Selective, Prostate-Specific Antigen-Targeted Oncolytic Adenovirus, for the Treatment of Hormone-Refractory, Metastatic Prostate Cancer. Molecular Therapy, 14, 107-117.
[96] Nettelbeck, D. (2008) Cellular Genetic Tools to Control Oncolytic Adenoviruses for Virotherapy of Cancer. Journal of Molecular Medicine, 86, 363-377. http://dx.doi.org/10.1007/s00109-007-0291-1
[97] Kyo, S., Takakura, M., Fujiwara, T. and Inoue, M. (2008) Understanding and Exploiting hTERT Promoter Regulation for Diagnosis and Treatment of Human Cancers. Cancer Science, 99, 1528-1538. http://dx.doi.org/10.1111/j.1349-7006.2008.00878.x
[98] De Benedetti, A. and Graff, J. (2004) eIF-4E Expression and Its Role in Malignancies and Metastases. Oncogene, 23, 3189-3199. http://dx.doi.org/10.1038/sj.onc.1207545
[99] Bilanges, B. and Stokoe, D. (2007) Mechanisms of Translational Deregulation in Human Tumors and Therapeutic Intervention Strategies. Oncogene, 26, 5973-5990.
[100] Sonenberg, N. and Hinnebusch, A. (2009) Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets. Cell, 136, 731-745. http://dx.doi.org/10.1016/j.cell.2009.01.042
[101] Pickering, B. and Willis, A. (2005) The Implications of Structured 5’ Untranslated Regions on Translation and Disease. Seminars in Cell & Developmental Biology, 16, 39-47.
[102] Watkins, S. and C. Norbury, C. (2002) Translation Initiation and Its Deregulation during Tumorigenesis. British Journal of Cancer, 86, 1023-1027. http://dx.doi.org/10.1038/sj.bjc.6600222
[103] Berkel, H., Turbat-Herrera, E., Shi, R. and Benedetti, A. (2001) Expression of the Translation Initiation Factor eIF4E in the Polyp-Cancer Sequence in the Colon. Cancer Epidemiology, Biomarkers & Prevention, 10, 663-666.
[104] Mamane, Y., Petroulakis, E., Rong, L., Yoshida, K., Ler, L.W. and Sonenberg, N. (2004) eIF4E—From Translation to Transformation. Oncogene, 23, 3172-3179. http://dx.doi.org/10.1038/sj.onc.1207549
[105] Lee, C.Y., Bu, L.X., De Benedetti, A., Williams, B.J., Rennie, P.S. and Jia, W.W. (2010) Transcriptional and Translational Dual-Regulated Oncolytic Herpes Simplex Virus Type 1 for Targeting Prostate Tumors. Molecular Therapy: The Journal of the American Society of Gene Therapy, 18, 929-935. http://dx.doi.org/10.1038/mt.2010.26
[106] Sacks, W., Greene, C., Aschman, D. and Schaffer, P. (1985) Herpes Simplex Virus Type 1 ICP27 Is an Essential Regulatory Protein. Journal of Virology, 55, 796-805.
[107] Zhang, J., Thomas, T., Kasper, S. and Matusik, R. (2000) A Small Composite Probasin Promoter Confers High Levels of Prostate-Specific Gene Expression through Regulation by Androgens and Glucocorticoids in Vitro and in Vivo. Endocrinology, 141, 4698-4710.
[108] Chlebova, K., Bryja, V., Dvorak, P., Kozubik, A., Wilcox, W.R. and Krejci, P. (2008) High Molecular Weight FGF2: The Biology of a Nuclear Growth Factor. Cellular and Molecular Life Sciences, 66, 225-235. http://dx.doi.org/10.1007/s00018-008-8440-4
[109] Mita, A.C., Mita, M.M., Nawrocki, S. and Giles, F.J. (2008) Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics. Clinical Cancer Research, 14, 5000-5005.
[110] Ryan, B.M., Donovan, N.O. and Duffy, M.J. (2009) Survivin: A New Target for Anti-Cancer Therapy. Cancer Treatment Reviews, 35, 553-562. http://dx.doi.org/10.1016/j.ctrv.2009.05.003
[111] Pennati, M., Folini, M. and Zaffaroni, N. (2007) Targeting Survivin in Cancer Therapy: Fulfilled Promises and Open Questions. Carcinogenesis, 28, 1133-1139.
[112] Fukuda, S. and Pelus, L.M. (2006) Survivin, a Cancer Target with an Emerging Role in Normal Adult Tissues. Molecular Cancer Therapeutics, 5, 1087-1098. http://dx.doi.org/10.1158/1535-7163.MCT-05-0375
[113] Mull, A.N., Klar, A. and Navara, C.S. (2014) Differential Localization and High Expression of SURVIVIN Splice Variants in Human Embryonic Stem Cells but Not in Differentiated Cells Implicate a Role for SURVIVIN in Pluripotency. Stem Cell Research, 12, 539-549.
[114] Hernandez, J.M., Farma, J.M., Coppola, D., Hakam, A., Fulp, W.J., Chen, D.T., Siegel, E.M., Yeatman, T.J. and Shibata, D. (2011) Expression of the Antiapoptotic Protein Survivin in Colon Cancer. Clinical Colorectal Cancer, 10, 188-193. http://dx.doi.org/10.1016/j.clcc.2011.03.014
[115] Krieg, A., Werner, T.A., Verde, P.E., Stoecklein, N.H. and Knoefel, W.T. (2013) Prognostic and Clinicopathological Significance of Survivin in Colorectal Cancer: A Meta-Analysis. PLoS ONE, 8, e65338. http://dx.doi.org/10.1371/journal.pone.0065338
[116] Kawasaki, H., Altieri, D.C., Lu, C.D., Toyoda, M., Tenjo, T. and Tanigawa, N. (1998) Inhibition of Apoptosis by Survivin Predicts Shorter Survival Rates in Colorectal Cancer. Cancer Research, 58, 5071-5074.
[117] Li, F. and Altieri, D. (1999) Transcriptional Analysis of Human Survivin Gene Expression. Biochemical Journal, 344, 305-311. http://dx.doi.org/10.1042/0264-6021:3440305
[118] Kamizono, J., Nagano, S., Murofushi, Y., Komiya, S., Fujiwara, H., Matsuishi, T. and Kosai, K. (2005) Survivin-Responsive Conditionally Replicating Adenovirus Exhibits Cancer-Specific and Efficient Viral Replication. Cancer Research, 65, 5284-5291. http://dx.doi.org/10.1158/0008-5472.CAN-04-2657
[119] Zhu, Z.B., Makhija, S.K., Lu, B., Wang, M., Kaliberova, L., Liu, B., Rivera, A.A., Nettelbeck, D.M., Mahasreshti, P.J., Leath III, C.A., Barker, S., Yamaoto, M., Li, F., Alvarez, R.D. and Curiel, D.T. (2004) Transcriptional Targeting of Tumors with a Novel Tumor-Specific Survivin Promoter. Cancer Gene Therapy, 11, 256-262. http://dx.doi.org/10.1038/sj.cgt.7700679
[120] Ulasov, I., Sonabend, A., Nandi, S., Khramtsov, A., Han, Y. and Lesniak, M. (2009) Combination of Adenoviral Virotherapy and Temozolomide Chemotherapy Eradicates Malignant Glioma through Autophagic and Apoptotic Cell Death in Vivo. British Journal of Cancer, 100, 1154-1164.
[121] Ahn, B.C., Ronald, J.A., Kim, Y.I., Katzenberg, R., Singh, A., Paulmurugan, R., Ray, S., Hofmann, L.V. and Gambhir, S.S. (2011) Potent, Tumor-Specific Gene Expression in an Orthotopic Hepatoma Rat Model Using a Survivin-Targeted, Amplifiable Adenoviral Vector. Gene Therapy, 18, 606-612. http://dx.doi.org/10.1038/gt.2011.5
[122] Okhi, R., Tsurimoto, T and Ishikawa, F. (2001) In Vitro Reconstitution of the End Replication Problem. Molecular Cell Biology, 21, 5753-5766. http://dx.doi.org/10.1128/MCB.21.17.5753-5766.2001
[123] Cong, Y.S., Wen, J. and Bacchetti, S. (1999) The Human Telomerase Catalytic Subunit hTERT: Organization of the Gene and Characterization of the Promoter. Human Molecular Genetics, 8, 137-142. http://dx.doi.org/10.1093/hmg/8.1.137
[124] Harley, C.B. (2008) Telomerase and Cancer Therapeutics. Nature Reviews Cancer, 8, 167-179. http://dx.doi.org/10.1038/nrc2275
[125] Gellert, G.C., Jackson, J.R., Dikmen, Z.G., Wright, W.E. and Shay, J.W. (2005) Telomerase as a Therapeutic Target in Cancer. Drug Discovery Today: Disease Mechanisms, 2, 159-164.
[126] Gertler, R., Rosenberg, R., Stricker, D., Friederichs, J., Hoos, A., Werner, M., Ulm, K., Holzmann, B., Nekarda, H. and Siewert, J.-R. (2004) Telomere Length and Human Telomerase Reverse Transcriptase Expression as Markers for Progression and Prognosis of Colorectal Carcinoma. Journal of Clinical Oncology, 22, 1807-1814. http://dx.doi.org/10.1200/JCO.2004.09.160
[127] Bertorelle, R., Briarava, M., Rampazzo, E., Biasini, L., Agostini, M., Maretto, I., Lonardi, S., Friso, M.L., Mescoli, C., Zagonel, V., Nitti, D., De Rossi, A. and Pucciarelli, S. (2013) Telomerase Is an Independent Prognostic Marker of Overall Survival in Patients with Colorectal Cancer. British Journal of Cancer, 108, 278-284. http://dx.doi.org/10.1038/bjc.2012.602
[128] Daniel, M., Peek, G.W. and Tollefsbol, T.O. (2012) Regulation of the Human Catalytic Subunit of Telomerase (hTERT). Gene, 498, 135-146. http://dx.doi.org/10.1016/j.gene.2012.01.095
[129] Poole, J.C., Andrews, L.G. and Tollefsbol, T.O. (2001) Activity, Function, and Gene Regulation of the Catalytic Subunit of Telomerase (hTERT). Gene, 269, 1-12. http://dx.doi.org/10.1016/S0378-1119(01)00440-1
[130] Janknecht, R. (2004) On the Road to Immortality: hTERT Upregulation in Cancer Cells. FEBS Letters, 564, 9-13. http://dx.doi.org/10.1016/S0014-5793(04)00356-4
[131] Kyo, S., Takakura, M., Taira, T., Kanaya, T., Itoh, H., Yutsudo, M., Ariga, H. and Inoue, M. (2000) Sp1 Cooperates with c-Myc to Activate Transcription of the Human Telomerase Reverse Transcriptase Gene (hTERT). Nucleic Acids Research, 28, 669-677. http://dx.doi.org/10.1093/nar/28.3.669
[132] Huang, T.G.G., Savontaus, M.J., Shinozaki, K., Sauter, B.V. and Woo, S.L. (2003) Telomerase-Dependent Oncolytic Adenovirus for Cancer Treatment. Gene Therapy, 10, 1241-1247.
[133] Taki, M., Kagawa, S., Nishizaki, M., Mizuguchi, H., Hayakawa, T., Kyo, S., Nagai, K., Urata, Y., Tanaka, N. and Fujiwara, T. (2005) Enhanced oncolysis by a Tropism-Modified Telomerase-Specific Replication-Selective Adenoviral Agent OBP-405 (“Telomelysin-RGD”). Oncogene, 24, 3130-3140.
[134] Kawashima, T. (2004) Telomerase-Specific Replication-Selective Virotherapy for Human Cancer. Clinical Cancer Research, 10, 285-292. http://dx.doi.org/10.1158/1078-0432.CCR-1075-3
[135] Nemunaitis, J., Tong, A.W., Nemunaitis, M., Senzer, N., Phadke, A.P., Bedell, C., Adams, N., Zhang, Y.A., Maples, P.B., Chen, S., Pappen, B., Burke, J., Ichimaru, D., Urata, Y. and Fujiwara, T. (2010) A Phase I Study of Telomerase-Specific Replication Competent Oncolytic Adenovirus (Telomelysin) for Various Solid Tumors. Molecular Therapy, 18, 429-434. http://dx.doi.org/10.1038/mt.2009.262
[136] Malumbres, M. and Barbacid, M. (2003) RAS Oncogenes: The First 30 Years. Nature Reviews Cancer, 3, 459-465. http://dx.doi.org/10.1038/nrc1097
[137] Downward, J. (2003) Targeting RAS Signaling Pathways in Cancer Therapy. Nature Reviews Cancer, 3, 11-22. http://dx.doi.org/10.1038/nrc969
[138] Rose J.S., Serna, D.S., Martin, L.K., Li, X., Weatherby, L.M., Abdel-Misih, A., Zhao, W. and Bekaii-Saab, T. (2012) Influence of KRAS Mutation Status in Metachronous and Synchronous Metastatic Colorectal Adenocarcinoma. Cancer, 118, 6243-6252. http://dx.doi.org/10.1002/cncr.27666
[139] van Houdt, W.J., Hoogwater, F.J.H., de Bruijn, M.T., Emmink, B.L., Nijkamp, M.W., Raats, D.A.E., van der Groep, P., van Diest, P., Rinkes, I.H.M.B. and Kranenburg, O. (2010) Oncogenic KRAS Desensitizes Colorectal Tumor Cells to Epidermal Growth Factor Receptor Inhibition and Activation. Neoplasia, 6, 443-452.
[140] Rajalingnam, K., Schreck, R., Rapp, U.R. and Albert, S. (2007) Ras Oncogenes and Their Downstream Targets. Biochimica et Biophysica Acta, 1773, 1177-1195.
[141] Karapetis, C.S., Khambata-Ford, S., Jonker, D.J., O’Callaghan, C.J., Tu, D., Tebbutt, N.C., Simes, R.J., Chalchal, H., Shapiro, J.D., Robitaille, S., Price, T.J., Shepherd, L., Au, H-J.J., Langer, D., Moore, M.J. and Zalcberg, J.R. (2008) K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer. The New England Journal of Medicine, 359, 1757-1765. http://dx.doi.org/10.1056/NEJMoa0804385
[142] Andreyev, H.J., Norman, A.R., Cunningham, D., Oates, J.R. and Clarke, P.A. (1998). Kirsten ras Mutations in Patients with Colorectal Cancer: The Multicenter “RASCAL” Study. Journal of the National Cancer Institute, 90, 675-684. http://dx.doi.org/10.1093/jnci/90.9.675
[143] Neumann, J., Zeindl-Eberhart, E., Kirchner, T. and Jung, A. (2009) Frequency and Type of KRAS Mutations in Routine Diagnostic Analysis of Metastatic Colorectal Cancer. Pathology—Research and Practice, 205, 858-862. http://dx.doi.org/10.1016/j.prp.2009.07.010
[144] Riely, G.J., Kris, M.G., Rosenbaum, D., Marks, J., Li, A., Chitale, D.A., Nafa, K., Riedel, E.R., Hsu, M., Pao, W., Miller, V.A. and Ladanyi, M. (2008) Frequency and Distinctive Spectrum of KRAS Mutations in Never Smokers with Lung Adenocarcinoma. Clinical Cancer Research, 14, 5731-5734.
[145] Roberts, M.S., Lorence, R.M., Groene, W.S. and Bamat, M.K. (2006) Naturally Oncolytic Viruses. Current Opinion in Molecular Therapeutics, 8, 314-321.
[146] Comins, C., Heinemann, L., Harrington, K., Melcher, A., De Bono, J. and Pandha, H. (2008) Reovirus: Viral Therapy for Cancer “as Nature Intended”. Clinical Oncology, 20, 548-554.
[147] Strong, J.E., Coffey, M.C., Tang, D., Sabinin, P. and Lee, P.W. (1998) The Molecular Basis of Viral Oncolysis: Usurpation of the Ras Signaling Pathway by Reovirus. The EMBO Journal, 17, 3351-3362. http://dx.doi.org/10.1093/emboj/17.12.3351
[148] Maitra, R., Ghalib, M.H. and Goel, S. (2012) Reovirus: A Targeted Therapeutic—Progress and Potential. Molecular Cancer Research, 10, 1514-1525. http://dx.doi.org/10.1158/1541-7786.MCR-12-0157
[149] Gollamudi, R., Ghalib, M.H., Desai, K.K., Chaudhary, I., Wong, B., Einstein, M., Coffey, M., Gill, G.M., Mettinger, K., Mariadason, J.M., Mani, S. and Goel, S. (2010) Intravenous Administration of Reolysin?, a Live Replication Competent RNA Virus Is Safe in Patients with Advanced Solid Tumors. Investigational New Drugs, 28, 641-649. http://dx.doi.org/10.1007/s10637-009-9279-8
[150] Galanis, E., Markovic, S.N., Suman, V.J., Nuovo, G.J., Vile, R.G., Kottke, T.J., Nevala, W.K., Thompson, M.A., Lewis, J.E., Rumilla, K.M., Roulstone, V., Harrington, K., Linette, G.P., Maples, W.J., Coffey, M., Zweibel, J. and Kendra, K. (2012) Phase II Trial of Intravenous Administration of REOLYSIN? (Reovirus Serotype-3-Dearing Strain) in Patients with Metastatic Melanoma. Molecular Therapy, 20, 1998-2003. http://dx.doi.org/10.1038/mt.2012.146
[151] Vermeulen, L., De Sousa, E., Melo, F., van der Heijden, M., Cameron, K., de Jong, J.H., Borovski, T., Tuynman, J.B., Todaro, M., Merz, C., Rodermond, H., Sprick, M.R., Kemper, K., Richel, D.J., Stassi, G. and Medema, J.P. (2010) Wnt Activity Defines Colon Cancer Stem Cells and Is Regulated by the Microenvironment. Nature Cell Biology, 12, 468-476. http://dx.doi.org/10.1038/ncb2048
[152] Suzuki, H., Watkins, D.N., Jair, K.-W.W., Schuebel, K.E., Markowitz, S.D., Chen, W.D., Pretlow, T.P., Yang, B., Akiyama, Y., van Engeland, M., Toyota, M., Tokino, T., Hinoda, Y., Imai, K., Herman, J.G. and Baylin, S.B. (2004) Epigenetic Inactivation of SFRP Genes Allows Constitutive WNT Signaling in Colorectal Cancer. Nature Genetics, 36, 417-422. http://dx.doi.org/10.1038/ng1330
[153] Clevers, H. (2006) Wnt/β-Catenin Signaling in Development and Disease. Cell, 127, 469-480. http://dx.doi.org/10.1016/j.cell.2006.10.018
[154] Segditsas, S. and Tomlinson, I. (2006) Colorectal Cancer and Genetic Alterations in the Wnt Pathway. Oncogene, 25, 7531-7537. http://dx.doi.org/10.1038/sj.onc.1210059
[155] Clevers, H. and Nusse, R. (2012) Wnt/β-Catenin Signaling and Disease. Cell, 149, 1192-1205. http://dx.doi.org/10.1016/j.cell.2012.05.012
[156] Li, V.S., Ng, S.S., Boersema, P.J., Low, T.Y., Karthaus, W.R., Gerlach, J.P., Mohammed, S., Heck, A.J.R., Maurice, M.M., Mahmoudi, T. and Clevers, H. (2012) Wnt Signaling through Inhibition of β-Catenin Degradation in an Intact Axin1 Complex. Cell, 149, 1245-1256.
[157] Aberle, H., Bauer, A., Stappert, J. Kispert, A. and Kemler, R. (1997) β-Catenin Is a Target for the Ubiquitin-Proteasome Pathway. The EMBO Journal, 16, 3797-3804.
[158] Narayan, S. and Roy, D. (2003) Role of APC and DNA Mismatch Repair Genes in the Development of Colorectal Cancers. Molecular Cancer, 2, 15 p. http://www.molecular-cancer.com/content/2/1/41
[159] Naik, S. and Piwnica-Worms, D. (2007) Real-Time Imaging of β-Catenin Dynamics in Cells and Living Mice. Proceedings of the National Academy of Sciences of the United States of America, 44, 17465-17470. http://dx.doi.org/10.1073/pnas.0704465104
[160] Sprowl, S. and Waterman, M.L. (2013) Past Visits Present: TCF/LEFs Partner with ATFs for β-Catenin-Independent Activity. PLoS Genetics, 9, e1003745. http://dx.doi.org/10.1371/journal.pgen.1003745
[161] Daniels, D.L. and Weis, W.I. (2005) β-Catenin Directly Displaces Groucho/TLE Repressors from Tcf/Lef in Wnt-Mediated Transcription Activation. Nature Structural and Molecular Biology, 12, 364-371. http://dx.doi.org/10.1038/nsmb912
[162] Galiatsatos, P. and Foulkes, W.D. (2006) Familial Adematous Polyposis. The American Journal of Gastroenterology, 101, 385-398. http://dx.doi.org/10.1111/j.1572-0241.2006.00375.x
[163] Fearnhead, N.S., Britton, M.P. and Bodmer, W.F. (2001) The ABC of APC. Human Molecular Genetics, 10, 721-733. http://dx.doi.org/10.1093/hmg/10.7.721
[164] Fuerer, C. and Iggo, R. (2004) 5-Fluorocytosine Increases the Toxicity of Wnt-Targeting Replicating Adenoviruses That Express Cytosine Deaminase as a Late Gene. Gene Therapy, 11, 142-151. http://dx.doi.org/10.1038/sj.gt.3302148
[165] Toth, K., Djeha, H., Ying, B., Tollefson, A.E., Kuppuswamy, M., Doronin, K., Krajcsi, P., Lipinski, K., Wrighton, C.J. and Wold, W.S. (2004) An Oncolytic Adenovirus Vector Combining Enhanced Cell-to-Cell Spreading, Mediated by the ADP Cytolytic Protein, with Selective Replication in Cancer Cells with Deregulated Wnt Signaling. Cancer Research, 64, 3638-3644. http://dx.doi.org/10.1158/0008-5472.CAN-03-3882
[166] Abbosh, P.H., Li, X., Li, L., Gardner, T.A., Kao, C. and Nephew, K.P. (2007) A Conditionally Replicative, Wnt/β-Catenin Pathway-Based Adenovirus Therapy for Anaplastic Thyroid Cancer. Cancer Gene Therapy, 14, 399-408. http://dx.doi.org/10.1038/sj.cgt.7701024
[167] Kuroda, T., Rabkin, S.D. and Martuza, R.L. (2006) Effective Treatment of Tumors with Strong Beta-Catenin/T-Cell Factor Activity by Transcriptionally Targeted Oncolytic Herpes Simplex Virus Vector. Cancer Research, 66, 10127-10135. http://dx.doi.org/10.1158/0008-5472.CAN-06-2744
[168] Pol, J.G., Rességuier, J. and Lichty, B.D. (2011) Oncolytic Viruses: A Step into Cancer Immunotherapy. Virus Adaptation and Treatment, 2, 1-21.
[169] Heo, J., Reid, T., Ruo, L., Breitbach, C.J., Rose, S., Bloomston, M., Cho, M., Lim, H.Y., Chung, H.C., Kim, C.W., Burke, J., Lencioni, R., Hickman, T., Moon, A., Lee, Y.S., Kim, M.K., Daneshmand, M., Dubois, K., Longpre, L., Ngo, M., Rooney, C., Bell, J.C., Rhee, B.-G., Patt, R., Hwang, T.-H. and Kirn, D.H. (2013) Randomized Dose-Finding Clinical Trial of Oncolytic Immunotherapeutic Vaccinia JX-594 in Liver Cancer. Nature Medicine, 19, 329-338. http://dx.doi.org/10.1038/nm.3089
[170] Wang, C., Xie, J., Guo, J., Manning, H.C., Gore, J.C. and Guo, N. (2012) Evaluation of CD44 and CD133 as Cancer Stem Cell Markers for Colorectal Cancer. Oncology Reports, 28, 1301-1308.
[171] Koltsova, E.K. and Grivennikov, S.I. (2014) IL-22 Gets to the Stem of Colorectal Cancer. Immunity, 40, 639-641. http://dx.doi.org/10.1016/j.immuni.2014.04.014
[172] Todaro, M., Gaggianesi, M., Catalano, V., Benfante, A., Iovino, F., Biffoni, M., Apuzzo, T., Sperduti, I., Volpe, S., Cocorullo, G., Gulotta, G., Dieli, F., Maria, R.D. and Stassi, G. (2014) CD44v6 Is a Marker of Constitutive and Reprogrammed Cancer Stem Cells Driving Colon Cancer Metastasis. Cancer Stem Cell, 3, 342-356. http://dx.doi.org/10.1016/j.stem.2014.01.009
[173] Bach, P., Abel, T., Hoffmann, C., Gal, A., Braun, G., Voelker, I., Ball, C.R., Johnston, I.C., Lauer, U.M., Herold-Mende, C., Mühlebach, M.D., Glimm, H. and Buchholz, C.J. (2013) Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus. Cancer Research, 73, 865-874.
[174] Ajayyousi, G., Abdulkarim, M., Griffiths, P. and Gumbleton, M. (2012) Pharmaceutical Nanoparticles and the Mucin Biopolymer Barrier. Bioimpacts, 2, 173-174.

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