Clinical and Translational Oncology

, Volume 20, Issue 5, pp 570–575 | Cite as

Ki67 targeted strategies for cancer therapy

  • C. Yang
  • J. Zhang
  • M. Ding
  • K. Xu
  • L. Li
  • L. Mao
  • J. Zheng
Review Article


Ki67 is a well-known proliferation marker for the evaluation of cell proliferation. Numerous studies have indicated that Ki67 index independently predicts cancer progression. Moreover, because Ki67 is highly expressed in malignant cells but almost could not be detected in normal cells, it has become a promising target for cancer therapy. In this review, we summarize recent advances in Ki67 targeted cancer therapy. In particular, we highlight recent development on the exploitation of Ki67 promoter to drive the expression of siRNAs or therapeutic genes in cancer cells specifically. The use of Ki67 as an attractive target opens a new avenue for cancer therapy.


Ki67 Gene therapy Renal cancer siRNA Target therapy Proliferation 


Compliance with ethical standards


This study was funded by grants from Jiangsu Province Science Foundation (No. BK2007032), Project of Invigorating Health Care through Science, Technology and Education, and Jiangsu Provincial Medical Youth Talent.

Conflict of interest

All authors declare no conflict of interest.

Research involving human participants and/or animals

Not applicable.

Informed consent

Not applicable.


  1. 1.
    Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182(3):311–22.CrossRefPubMedGoogle Scholar
  2. 2.
    Isola J, Helin H, Kallioniemi OP. Immunoelectron-microscopic localization of a proliferation-associated antigen Ki-67 in MCF-7 cells. Histochem J. 1990;22(9):498–506.CrossRefPubMedGoogle Scholar
  3. 3.
    Verheijen R, Kuijpers HJ, Schlingemann RO, Boehmer AL, van Driel R, Brakenhoff GJ, et al. Ki-67 detects a nuclear matrix-associated proliferation-related antigen. I. Intracellular localization during interphase. J Cell Sci. 1989;92(Pt 1):123–30.PubMedGoogle Scholar
  4. 4.
    Schluter C, Duchrow M, Wohlenberg C, Becker MH, Key G, Flad HD, et al. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol. 1993;123(3):513–22.CrossRefPubMedGoogle Scholar
  5. 5.
    Fonatsch C, Duchrow M, Rieder H, Schlüter C, Gerdes J. Assignment of the human Ki-67 gene (MK167) to 10q25-qter. Genomics. 1991;11(2):476–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Duchrow M, Schluter C, Wohlenberg C, Flad HD, Gerdes J. Molecular characterization of the gene locus of the human cell proliferation-associated nuclear protein defined by monoclonal antibody Ki-67. Cell Prolif. 1996;29(1):1–12.CrossRefPubMedGoogle Scholar
  7. 7.
    Du Manoir S, Guillaud P, Camus E, Seigneurin D, Brugal G. Ki-67 labeling in postmitotic cells defines different Ki-67 pathways within the 2c compartment. Cytometry. 1991;12(5):455–63.CrossRefPubMedGoogle Scholar
  8. 8.
    Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133(4):1710–5.PubMedGoogle Scholar
  9. 9.
    Rioux-Leclercq N, Turlin B, Bansard J, Patard J, Manunta A, Moulinoux JP, et al. Value of immunohistochemical Ki-67 and p53 determinations as predictive factors of outcome in renal cell carcinoma. Urology. 2000;55(4):501–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Visapää H, Bui M, Huang Y, Seligson D, Tsai H, Pantuck A, et al. Correlation of Ki-67 and gelsolin expression to clinical outcome in renal clear cell carcinoma. Urology. 2003;61(4):845–50.CrossRefPubMedGoogle Scholar
  11. 11.
    Karamitopoulou E, Perentes E, Tolnay M, Probst A. Prognostic significance of MIB-1, p53, and bcl-2 immunoreactivity in meningiomas. Hum Pathol. 1998;29(2):140–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Geyer FC, Rodrigues DN, Weigelt B, Reis-Filho JS, et al. Molecular classification of estrogen receptor-positive/luminal breast cancers. Adv Anat Pathol. 2012;19(1):39–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Zizi-Sermpetzoglou A, Moustou E, Petrakopoulou N, Arkoumani E, Tepelenis N, Savvaidou V, et al. Atypical polypoid adenomyoma of the uterus. A case report and a review of the literature. Eur J Gynaecol Oncol. 2012;33(1):118–21.PubMedGoogle Scholar
  14. 14.
    Zini L, Porpiglia F, Fassnacht M. Contemporary management of adrenocortical carcinoma. Eur Urol. 2011;60(5):1055–65.CrossRefPubMedGoogle Scholar
  15. 15.
    Viale G. Pathological work up of the primary tumor: getting the proper information out of it. Breast. 2011;20(Suppl 3):S82–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Bertolini M, Sobue T, Thompson A, Dongari-Bagtzoglou A. Chemotherapy induces oral mucositis in mice without additional noxious stimuli. Transl Oncol. 2017;10(4):612–20.CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Ibrahim T, Farolfi A, Scarpi E, Mercatali L, Medri L, Ricci M, et al. Hormonal receptor, human epidermal growth factor receptor-2, and Ki67 discordance between primary breast cancer and paired metastases: clinical impact. Oncology. 2013;84(3):150–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Blancato J, Singh B, Liu A, Liao DJ, Dickson RB. Correlation of amplification and overexpression of the c-myc oncogene in high-grade breast cancer: FISH, in situ hybridisation and immunohistochemical analyses. Br J Cancer. 2004;90(8):1612–9.CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Chlebowski RT, Col N, Winer EP, Collyar DE, Cummings SR, Vogel VG 3rd, et al. American Society of Clinical Oncology technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol. 2002;20(15):3328–43.CrossRefPubMedGoogle Scholar
  20. 20.
    Nagao K, Yamamoto Y, Hara T, Komatsu H, Inoue R, Matsuda K, et al. Ki67 and BUBR1 may discriminate clinically insignificant prostate cancer in the PSA range < 4 ng/ml. Jpn J Clin Oncol. 2011;41(4):555–64.CrossRefPubMedGoogle Scholar
  21. 21.
    Zheng K, Zhu W, Tan J, Wu W, Yang S, Zhang J. Retrospective analysis of a large patient sample to determine p53 and Ki67 expressions in renal cell carcinoma. J BUON. 2014;19(2):512–6.PubMedGoogle Scholar
  22. 22.
    Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep. 2015;11(3):1566–72.CrossRefPubMedGoogle Scholar
  23. 23.
    Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. N Engl J Med. 2015;373(5):438–47.CrossRefPubMedGoogle Scholar
  24. 24.
    Kennedy BW. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn’s disease. N Engl J Med. 2015;372(25):2461.CrossRefPubMedGoogle Scholar
  25. 25.
    Wheeler TM, Leger AJ, Pandey SK, MacLeod AR, Nakamori M, Cheng SH, et al. Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature. 2012;488(7409):111–5.CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Buller HR, Bethune C, Bhanot S, Gailani D, Monia BP, Raskob GE, et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015;372(3):232–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, et al. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014;371(23):2200–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Natale R, Blackhall F, Kowalski D, Ramlau R, Bepler G, Grossi F, et al. Evaluation of antitumor activity using change in tumor size of the surviving antisense oligonucleotide LY2181308 in combination with docetaxel for second-line treatment of patients with non-small-cell lung cancer: a randomized open-label phase II study. J Thorac Oncol. 2014;9(11):1704–8.CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, et al. First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov. 2012;2(8):694–705.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Laskin JJ, Nicholas G, Lee C, Gitlitz B, Vincent M, Cormier Y, et al. Phase I/II trial of custirsen (OGX-011), an inhibitor of clusterin, in combination with a gemcitabine and platinum regimen in patients with previously untreated advanced non-small cell lung cancer. J Thorac Oncol. 2012;7(3):579–86.CrossRefPubMedGoogle Scholar
  31. 31.
    Kausch I, Lingnau A, Endl E, Sellmann K, Deinert I, Ratliff TL, et al. Antisense treatment against Ki-67 mRNA inhibits proliferation and tumor growth in vitro and in vivo. Int J Cancer. 2003;105(5):710–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Kausch I, Jiang H, Ewerdwalbesloh N, Doehn C, Krüger S, Sczakiel G, et al. Inhibition of Ki-67 in a renal cell carcinoma severe combined immunodeficiency disease mouse model is associated with induction of apoptosis and tumour growth inhibition. BJU Int. 2005;95(3):416–20.CrossRefPubMedGoogle Scholar
  33. 33.
    Li XQ, Pei DS, Qian GW, Yin XX, Cheng Q, Li LT, et al. The effect of methylated oligonucleotide targeting Ki-67 gene in human 786-0 renal carcinoma cells. Tumour Biol. 2011;32(5):863–72.CrossRefPubMedGoogle Scholar
  34. 34.
    Ratilainen T, Holmén A, Tuite E, Nielsen PE, Nordén B. Thermodynamics of sequence-specific binding of PNA to DNA. Biochemistry. 2000;39(26):7781–91.CrossRefPubMedGoogle Scholar
  35. 35.
    Thomas SM, Sahu B, Rapireddy S, Bahal R, Wheeler SE, Procopio EM, et al. Antitumor effects of EGFR antisense guanidine-based peptide nucleic acids in cancer models. ACS Chem Biol. 2013;8(2):345–52.CrossRefPubMedGoogle Scholar
  36. 36.
    Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C, et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature. 2015;518(7537):107–10.CrossRefPubMedGoogle Scholar
  37. 37.
    Hanvey JC, Peffer NJ, Bisi JE, Thomson SA, Cadilla R, Josey JA, et al. Antisense and antigene properties of peptide nucleic acids. Science. 1992;258(5087):1481–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Norton JC, Piatyszek MA, Wright WE, Shay JW, Corey DR. Inhibition of human telomerase activity by peptide nucleic acids. Nat Biotechnol. 1996;14(5):615–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Zheng JN, Sun YF, Pei DS, Liu JJ, Sun XQ, Chen JC, et al. Anti-Ki-67 peptide nucleic acid affects the proliferation and apoptosis of human renal carcinoma cells in vitro. Life Sci. 2005;76(16):1873–81.CrossRefPubMedGoogle Scholar
  40. 40.
    Wyatt CA, Geoghegan JC, Brinckerhoff CE. Short hairpin RNA-mediated inhibition of matrix metalloproteinase-1 in MDA-231 cells: effects on matrix destruction and tumor growth. Cancer Res. 2005;65(23):11101–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Zuckerman JE, Davis ME. Clinical experiences with systemically administered siRNA-based therapeutics in cancer. Nat Rev Drug Discov. 2015;14(12):843–56.CrossRefPubMedGoogle Scholar
  42. 42.
    Zheng JN, Ma TX, Cao JY, Sun XQ, Chen JC, Li W, et al. Knockdown of Ki-67 by small interfering RNA leads to inhibition of proliferation and induction of apoptosis in human renal carcinoma cells. Life Sci. 2006;78(7):724–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Zheng JN, Sun YF, Pei DS, Liu JJ, Ma TX, Han RF, et al. Treatment with vector-expressed small hairpin RNAs against Ki67 RNA-induced cell growth inhibition and apoptosis in human renal carcinoma cells. Acta Biochim Biophys Sin (Shanghai). 2006;38(4):254–61.CrossRefGoogle Scholar
  44. 44.
    Burnett JC, Rossi JJ. RNA-based therapeutics: current progress and future prospects. Chem Biol. 2012;19(1):60–71.CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Vaishnaw AK, Gollob J, Gamba-Vitalo C, Hutabarat R, Sah D, Meyers R, et al. A status report on RNAi therapeutics. Silence. 2010;1(1):14.CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Sepp-Lorenzino L, Ruddy M. Challenges and opportunities for local and systemic delivery of siRNA and antisense oligonucleotides. Clin Pharmacol Ther. 2008;84(5):628–32.CrossRefPubMedGoogle Scholar
  47. 47.
    Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009;8(2):129–38.CrossRefPubMedGoogle Scholar
  48. 48.
    Chen SH, Zhaori G. Potential clinical applications of siRNA technique: benefits and limitations. Eur J Clin Invest. 2011;41(2):221–32.CrossRefPubMedGoogle Scholar
  49. 49.
    Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK. RNA interference in the clinic: challenges and future directions. Nat Rev Cancer. 2011;11(1):59–67.CrossRefPubMedGoogle Scholar
  50. 50.
    Wu SY, Lopez-Berestein G, Calin GA, Sood AK. RNAi therapies: drugging the undruggable. Sci Transl Med. 2014;6(240):240.CrossRefGoogle Scholar
  51. 51.
    Ku SH, Kim K, Choi K, Kim SH, Kwon IC. Tumor-targeting multifunctional nanoparticles for siRNA delivery: recent advances in cancer therapy. Adv Healthc Mater. 2014;3(8):1182–93.CrossRefPubMedGoogle Scholar
  52. 52.
    Conde J, Artzi N. Are RNAi and miRNA therapeutics truly dead? Trends Biotechnol. 2015;33(3):141–4.CrossRefPubMedGoogle Scholar
  53. 53.
    Haussecker D. The business of RNAi therapeutics in 2012. Mol Ther Nucleic Acids. 2012;1:e8.CrossRefPubMedCentralPubMedGoogle Scholar
  54. 54.
    Vicentini FT, Borgheti-Cardoso LN, Depieri LV, de Macedo Mano D, Abelha TF, Petrilli R. Delivery systems and local administration routes for therapeutic siRNA. Pharm Res. 2013;30(4):915–31.CrossRefPubMedGoogle Scholar
  55. 55.
    Conde J, Edelman ER, Artzi N. Target-responsive DNA/RNA nanomaterials for microRNA sensing and inhibition: the jack-of-all-trades in cancer nanotheranostics? Adv Drug Deliv Rev. 2015;81:169–83.CrossRefPubMedGoogle Scholar
  56. 56.
    Zhou Y, Zhang C, Liang W. Development of RNAi technology for targeted therapy–a track of siRNA based agents to RNAi therapeutics. J Control Release. 2014;193:270–81.CrossRefPubMedGoogle Scholar
  57. 57.
    Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996;274(5286):373–6.CrossRefPubMedGoogle Scholar
  58. 58.
    Liu XY. Targeting gene-virotherapy of cancer and its prosperity. Cell Res. 2006;16(11):879–86.CrossRefPubMedGoogle Scholar
  59. 59.
    Yu DC, Chen Y, Dilley J, Li Y, Embry M, Zhang H, et al. Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel. Cancer Res. 2001;61(2):517–25.PubMedGoogle Scholar
  60. 60.
    Choi JW, Lee JS, Kim SW, Yun CO. Evolution of oncolytic adenovirus for cancer treatment. Adv Drug Deliv Rev. 2012;64(8):720–9.CrossRefPubMedGoogle Scholar
  61. 61.
    Rajecki M, Kanerva A, Stenman UH, Tenhunen M, Kangasniemi L, Särkioja M, et al. Treatment of prostate cancer with Ad5/3Delta24hCG allows non-invasive detection of the magnitude and persistence of virus replication in vivo. Mol Cancer Ther. 2007;6(2):742–51.CrossRefPubMedGoogle Scholar
  62. 62.
    Lei J, Li QH, Yang JL, Liu F, Wang L, Xu WM, et al. The antitumor effects of oncolytic adenovirus H101 against lung cancer. Int J Oncol. 2015;47(2):555–62.CrossRefPubMedGoogle Scholar
  63. 63.
    Freytag SO, Movsas B, Aref I, Stricker H, Peabody J, Pegg J, et al. Phase I trial of replication-competent adenovirus-mediated suicide gene therapy combined with IMRT for prostate cancer. Mol Ther. 2007;15(5):1016–23.CrossRefPubMedGoogle Scholar
  64. 64.
    Li JL, Liu HL, Zhang XR, Xu JP, Hu WK, Liang M, et al. A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients. Gene Ther. 2009;16(3):376–82.CrossRefPubMedGoogle Scholar
  65. 65.
    Nemunaitis J, Tong AW, Nemunaitis M, Senzer N, Phadke AP, Bedell C, et al. A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol Ther. 2010;18(2):429–34.CrossRefPubMedGoogle Scholar
  66. 66.
    Yang SW, Cody JJ, Rivera AA, Waehler R, Wang M, Kimball KJ, et al. Conditionally replicating adenovirus expressing TIMP2 for ovarian cancer therapy. Clin Cancer Res. 2011;17(3):538–49.CrossRefPubMedGoogle Scholar
  67. 67.
    Freytag SO, Stricker H, Lu M, Elshaikh M, Aref I, Pradhan D, et al. Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2014;89(2):268–76.CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Kanerva A, Nokisalmi P, Diaconu I, Koski A, Cerullo V, Liikanen I, et al. Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus. Clin Cancer Res. 2013;19(10):2734–44.CrossRefPubMedGoogle Scholar
  69. 69.
    Tong AW, Zhang YA, Nemunaitis J. Small interfering RNA for experimental cancer therapy. Curr Opin Mol Ther. 2005;7(2):114–24.PubMedGoogle Scholar
  70. 70.
    Chen RF, Li YY, Li LT, Cheng Q, Jiang G, Zheng JN. Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death. Mol Med Rep. 2015;11(3):2141–6.CrossRefPubMedGoogle Scholar
  71. 71.
    Toth K, Wold WS. Increasing the efficacy of oncolytic adenovirus vectors. Viruses. 2010;2(9):1844–66.CrossRefPubMedCentralPubMedGoogle Scholar
  72. 72.
    O’Shea CC. Viruses—seeking and destroying the tumor program. Oncogene. 2005;24(52):7640–55.CrossRefPubMedGoogle Scholar
  73. 73.
    Liu J, Fang L, Cheng Q, Li L, Su C, Zhang B, et al. Effects of G250 promoter controlled conditionally replicative adenovirus expressing Ki67-siRNA on renal cancer cell. Cancer Sci. 2012;103(10):1880–8.CrossRefPubMedGoogle Scholar
  74. 74.
    Zhang J, Ding M, Xu K, Mao L, Zheng J. shRNA-armed conditionally replicative adenoviruses: a promising approach for cancer therapy. Oncotarget. 2016;7:29824.PubMedCentralPubMedGoogle Scholar
  75. 75.
    Shay JW, Wright WE. Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov. 2006;5(7):577–84.CrossRefPubMedGoogle Scholar
  76. 76.
    Fang L, Cheng Q, Li W, Liu J, Li L, Xu K, et al. Antitumor activities of an oncolytic adenovirus equipped with a double siRNA targeting Ki67 and hTERT in renal cancer cells. Virus Res. 2014;181:61–71.CrossRefPubMedGoogle Scholar
  77. 77.
    Tian H, Qian GW, Li W, Chen FF, Di JH, Zhang BF, et al. A critical role of Sp1 transcription factor in regulating the human Ki-67 gene expression. Tumour Biol. 2011;32(2):273–83.CrossRefPubMedGoogle Scholar
  78. 78.
    Pei DS, Qian GW, Tian H, Mou J, Li W, Zheng JN. Analysis of human Ki-67 gene promoter and identification of the Sp1 binding sites for Ki-67 transcription. Tumour Biol. 2012;33(1):257–66.CrossRefPubMedGoogle Scholar
  79. 79.
    Chen F, Song J, Di J, Zhang Q, Tian H, Zheng J. IRF1 suppresses Ki-67 promoter activity through interfering with Sp1 activation. Tumour Biol. 2012;33(6):2217–25.CrossRefPubMedGoogle Scholar
  80. 80.
    Wang MJ, Pei DS, Qian GW, Yin XX, Cheng Q, Li LT, et al. p53 regulates Ki-67 promoter activity through p53- and Sp1-dependent manner in HeLa cells. Tumour Biol. 2011;32(5):905–12.CrossRefPubMedGoogle Scholar
  81. 81.
    Hoffmann D, Jogler C, Wildner O. Effects of the Ad5 upstream E1 region and gene products on heterologous promoters. J Gene Med. 2005;7(10):1356–66.CrossRefPubMedGoogle Scholar
  82. 82.
    Jiang G, Jiang AJ, Cheng Q, Tian H, Li LT, Zheng JN. A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis. Tumour Biol. 2013;34(2):1263–71.CrossRefPubMedGoogle Scholar
  83. 83.
    Jiang G, Yang CS, Xu D, Sun C, Zheng JN, Lei TC, et al. Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion. Br J Cancer. 2014;110(10):2496–505.CrossRefPubMedCentralPubMedGoogle Scholar
  84. 84.
    Nemunaitis J, Cunningham C, Tong A, Post L, Netto G, Paulson AS, et al. Pilot trial of intravenous infusion of a replication-selective adenovirus (ONYX-015) in combination with chemotherapy or IL-2 treatment in refractory cancer patients. Cancer Gene Ther. 2003;10(5):341–52.CrossRefPubMedGoogle Scholar
  85. 85.
    Reid T, Galanis E, Abbruzzese J, Sze D, Wein LM, Andrews J, et al. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res. 2002;62(21):6070–9.PubMedGoogle Scholar
  86. 86.
    Nemunaitis J, Cunningham C, Buchanan A, Blackburn A, Edelman G, Maples P, et al. Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther. 2001;8(10):746–59.CrossRefPubMedGoogle Scholar
  87. 87.
    Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff DD, Kirn DH. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med. 1997;3(6):639–45.CrossRefPubMedGoogle Scholar
  88. 88.
    Chu L, Gu J, Sun L, Qian Q, Qian C, Liu X. Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil. Gene Ther. 2008;15(7):484–94.CrossRefPubMedGoogle Scholar
  89. 89.
    Bramante S, Koski A, Liikanen I, Vassilev L, Oksanen M, Siurala M, et al. Oncolytic virotherapy for treatment of breast cancer, including triple-negative breast cancer. Oncoimmunology. 2016;5(2):e1078057.CrossRefPubMedGoogle Scholar
  90. 90.
    Liikanen I, Ahtiainen L, Hirvinen ML, Bramante S, Cerullo V, Nokisalmi P, et al. Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther. 2013;21(6):1212–23.CrossRefPubMedCentralPubMedGoogle Scholar
  91. 91.
    Jiang G, Sun C, Li RH, Wei ZP, Zheng JN, Liu YQ. Enhanced antitumor efficacy of a novel oncolytic adenovirus combined with temozolomide in the treatment of melanoma in vivo. J Cancer Res Clin Oncol. 2015;141(1):75–85.CrossRefPubMedGoogle Scholar
  92. 92.
    Wang W, Sima N, Kong D, Luo A, Gao Q, Liao S, et al. Selective targeting of HPV-16 E6/E7 in cervical cancer cells with a potent oncolytic adenovirus and its enhanced effect with radiotherapy in vitro and vivo. Cancer Lett. 2010;291(1):67–75.CrossRefPubMedGoogle Scholar
  93. 93.
    Wang H, Song X, Zhang H, Zhang J, Shen X, Zhou Y, et al. Potentiation of tumor radiotherapy by a radiation-inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts. Int J Cancer. 2012;130(2):443–53.CrossRefPubMedGoogle Scholar
  94. 94.
    Biroccio A, Leonetti C, Zupi G. The future of antisense therapy: combination with anticancer treatments. Oncogene. 2003;22(42):6579–88.CrossRefPubMedGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2017

Authors and Affiliations

  1. 1.Jiangsu Key Laboratory of Biological Cancer TherapyXuzhou Medical UniversityXuzhouChina
  2. 2.Department of Urinary SurgeryThe Affiliated Hospital of University Medical CollegeXuzhouChina

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