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Vector engineering, strategies and targets in cancer gene therapy

Cancer Gene Therapy volume 29, pages 402–417 (2022)Cite this article

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Abstract

Understanding the molecular basis of disease and the design of rationally designed molecular therapies has been the holy grail in the management of human cancers. Gene-based therapies are an important avenue for achieving a possible cure. Focused research in the last three decades has provided significant clues to optimize the potential of cancer gene therapy. The development of gene therapies with a high potential to kill the target cells at the lowest effective dose possible, the development of vectors with significant ability to target cancer-associated antigen, the application of adjunct therapies to target dysregulated microRNA, and embracing a hybrid strategy with a combination of gene therapy and low-dose chemotherapy in a disease-specific manner will be pivotal. This article outlines the advances and challenges in the field with emphasis on the biology and scope of vectors used for gene transfer, newer targets identified, and their outcome in preclinical and clinical studies.

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Fig. 1: Vectors for delivery of a therapeutic gene into a host cell.
Fig. 2: Mechanism of action of different suicide gene systems.
Fig. 3: Chimeric antigen receptor (CAR) vector.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal AJ. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. 2018;68:394–424.

    Google Scholar 

  2. Wang J, Lei K, Han F. Tumor microenvironment: recent advances in various cancer treatments. Eur Rev Med Pharm Sci. 2018;22:3855–64.

    Google Scholar 

  3. Schirrmacher V. From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol. 2019;54:407–19.

    CAS  PubMed  Google Scholar 

  4. Hardee CL, Arévalo-Soliz LM, Hornstein BD, Zechiedrich L. Advances in non-viral DNA vectors for gene therapy. Genes 2017;8:65.

    Article  PubMed Central  CAS  Google Scholar 

  5. Marofi F, Vahedi G, Biglari A, Esmaeilzadeh A, Athari SS. Mesenchymal stromal/stem cells: a new era in the cell-based targeted gene therapy of cancer. Front Immunol. 2017;8:1770.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Goncalves GAR, Paiva RMA. Gene therapy: advances, challenges and perspectives. Einstein. 2017;15:369–75.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 2019;20:e175–86.

    Article  CAS  PubMed  Google Scholar 

  8. Xia Y, Du Z, Wang X, Li X. Treatment of uterine sarcoma with rAd-p53 (gendicine) followed by chemotherapy: clinical study of TP53 gene therapy. Hum Gene Ther. 2018;29:242–50.

    Article  CAS  PubMed  Google Scholar 

  9. Lazzari C, Karachaliou N, Bulotta A, Viganó M, Mirabile A, Brioschi E, et al. Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer? Ther Adv Med Oncol. 2018;10:1758835918762094.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Chakraborty C, Sharma AR, Sharma G, Sarkar BK, Lee SS. The novel strategies for next-generation cancer treatment: miRNA combined with chemotherapeutic agents for the treatment of cancer. Oncotarget 2018;9:10164.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mali S. Delivery systems for gene therapy. Indian J Hum Genet. 2013;19:3–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. del Pozo-Rodríguez A, Solinís MÁ. Rodríguez-Gascón. Applications of lipid nanoparticles in gene therapy. Eur J Pharm Biopharm. 2016;109:184–93.

    Article  PubMed  CAS  Google Scholar 

  13. Ramamoorth M, Narvekar A. Non viral vectors in gene therapy-an overview. J Clin Diagn Res. 2015;9:GE01.

    PubMed  PubMed Central  Google Scholar 

  14. Zhou Z, Liu X, Zhu D, Wang Y, Zhang Z, Zhou X, et al. Nonviral cancer gene therapy: Delivery cascade and vector nanoproperty integration. Adv Drug Deliv Rev. 2017;115:115–54.

    Article  CAS  PubMed  Google Scholar 

  15. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15:541–55.

    Article  CAS  PubMed  Google Scholar 

  16. Malekshah OM, Chen X, Nomani A, Sarkar S, Hatefi A. Enzyme/prodrug systems for cancer gene therapy. Curr Pharm Rep. 2016;2:299–308.

    Article  CAS  Google Scholar 

  17. Barrangou R, Doudna JA. Applications of CRISPR technologies in research and beyond. Nat Biotechnol. 2016;34:933–41.

    Article  CAS  PubMed  Google Scholar 

  18. Sung YK, Kim SW. Recent advances in the development of gene delivery systems. Biomater Res. 2019;23:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nayerossadat N, Maedeh T, Ali PA. Viral and nonviral delivery systems for gene delivery. Adv Biomed Res. 2012;1:27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Pahle J, Walther W. Vectors and strategies for nonviral cancer gene therapy. Expert Opin Biol Ther. 2016;16:443–61.

    Article  CAS  PubMed  Google Scholar 

  21. Jiang C, Chen J, Li Z, Wang Z, Zhang W, Liu J. Recent advances in the development of polyethylenimine-based gene vectors for safe and efficient gene delivery. Expert Opin Drug Deliv. 2019;16:363–76.

    Article  CAS  PubMed  Google Scholar 

  22. Keles E, Song Y, Du D, Dong W-J, Lin Y. Recent progress in nanomaterials for gene delivery applications. Biomater Sci. 2016;4:1291–309.

    Article  CAS  PubMed  Google Scholar 

  23. Mandal H, Katiyar SS, Swami R, Kushwah V, Katare PB, Meka AK, et al. ε-Poly-l-Lysine/plasmid DNA nanoplexes for efficient gene delivery in vivo. Int J Pharm. 2018;542:142–52.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang T, Xue X, He D, Hsieh JT. A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA. Cancer Lett. 2015;365:156–65.

    Article  CAS  PubMed  Google Scholar 

  25. Dai Y, Zhang X. MicroRNA delivery with bioreducible polyethylenimine as a non-viral vector for breast cancer gene therapy. Macromol Biosci. 2019;19:e1800445.

    Article  PubMed  CAS  Google Scholar 

  26. Wang K, Kievit FM, Zhang M. Nanoparticles for cancer gene therapy: recent advances, challenges, and strategies. Pharm Res. 2016;114:56–66.

    Article  CAS  Google Scholar 

  27. Li HX, Zhao XY, Wang L, Wang YS, Kan B, Xu JR, et al. Antitumor effect of mSurvivinThr34–>Ala in murine colon carcinoma when administered intravenously. Med Oncol. 2010;27:1156–63.

    Article  CAS  PubMed  Google Scholar 

  28. Liu CH, Chern GJ, Hsu FF, Huang KW, Sung YC, Huang HC, et al. A multifunctional nanocarrier for efficient TRAIL-based gene therapy against hepatocellular carcinoma with desmoplasia in mice. Hepatology 2018;67:899–913.

    Article  CAS  PubMed  Google Scholar 

  29. Baig B, Halim SA, Farrukh A, Greish Y, Amin A. Current status of nanomaterial-based treatment for hepatocellular carcinoma. Biomed Pharmacother. 2019;116:108852.

    Article  CAS  PubMed  Google Scholar 

  30. Xin Y, Huang M, Guo WW, Huang Q, Zhang LZ, Jiang G. Nano-based delivery of RNAi in cancer therapy. Mol Cancer. 2017;16:134.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017;546:498–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang F, Li L, Piontek K, Sakaguchi M, Selaru FM. Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma. Hepatology 2018;67:940–54.

    Article  CAS  PubMed  Google Scholar 

  33. Khan N, Maurya S, Bammidi S, Jayandharan GR. AAV6 vexosomes mediate robust suicide gene delivery in a murine model of hepatocellular carcinoma. Mol Ther Methods Clin Dev. 2020;17:497–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Osman N, Kaneko K, Carini V, Saleem I. Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies. Expert Opin Drug Deliv. 2018;15:821–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lara-Guerra H, Roth JA. Gene therapy for lung cancer. Crit Rev Oncol. 2016;21:115–24.

    Article  Google Scholar 

  36. Lundstrom K. Self-replicating RNA Viruses for RNA therapeutics. Molecules 2018;23:3310.

    Article  PubMed Central  CAS  Google Scholar 

  37. Lundstrom K. Self-replicating RNA viral vectors in vaccine development and gene therapy. Future Virol. 2016;11:345–56.

    Article  CAS  Google Scholar 

  38. Gruntman AM, Flotte TR. The rapidly evolving state of gene therapy. FASEB J. 2018;32:1733–40.

    Article  CAS  PubMed  Google Scholar 

  39. Lundstrom K. RNA Viruses as tools in gene therapy and vaccine development. Genes 2019;10:189.

    Article  CAS  PubMed Central  Google Scholar 

  40. Vargas JE, Chicaybam L, Stein RT, Tanuri A, Delgado-Cañedo A, Bonamino MH. Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives. J Transl Med. 2016;14:1–15.

    Article  CAS  Google Scholar 

  41. Zhang J, Liu Y, Zang M, Zhu S, Chen B, Li S, et al. Lentivirus-mediated CDglyTK gene-modified free flaps by intra-artery perfusion show targeted therapeutic efficacy in rat model of breast cancer. BMC Cancer. 2019;19:1–11.

    Google Scholar 

  42. Matsunaga W, Ichikawa M, Nakamura A, Ishikawa T, Gotoh A. Lentiviral vector-mediated gene transfer in human bladder cancer cell lines. Anticancer Res. 2018;38:2015–20.

    CAS  PubMed  Google Scholar 

  43. Lopez-Gordo E, Podgorski II, Downes N, Alemany R. Circumventing antivector immunity: potential use of nonhuman adenoviral vectors. Hum Gene Ther. 2014;25:285–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wheeler LA, Manzanera AG, Bell SD, Cavaliere R, McGregor JM, Grecula JC, et al. Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. Neuro Oncol. 2016;18:1137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ehrke-Schulz E, Heinemann S, Schulte L, Schiwon M, Ehrhardt AJC. Adenoviral vectors armed with PAPILLOMAVIRUs oncogene specific CRISPR/Cas9 kill human-papillomavirus-induced cervical cancer cells. Cancers 2020;12:1934.

    Article  CAS  PubMed Central  Google Scholar 

  46. Westphal M, Yla-Herttuala S, Martin J, Warnke P, Menei P, Eckland D, et al. Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:823–33.

    Article  CAS  PubMed  Google Scholar 

  47. Catanzaro AT, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, et al. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector. J Infect Dis. 2006;194:1638–49.

    Article  CAS  PubMed  Google Scholar 

  48. Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005;16:149–56.

    Article  CAS  PubMed  Google Scholar 

  49. Trapani I. Adeno-associated viral vectors as a tool for large gene delivery to the retina. Genes 2019;10:287.

    Article  CAS  PubMed Central  Google Scholar 

  50. Luo J, Luo Y, Sun J, Zhou Y, Zhang Y, Yang X. Adeno-associated virus-mediated cancer gene therapy: current status. Cancer Lett. 2015;356:347–56.

    Article  CAS  PubMed  Google Scholar 

  51. Kotterman MA, Schaffer DV. Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet. 2014;15:445–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Carruthers KH, Metzger G, During MJ, Muravlev A, Wang C, Kocak E. Gene-directed enzyme prodrug therapy for localized chemotherapeutics in allograft and xenograft tumor models. Cancer Gene Ther. 2014;21:434–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Dhungel B, Jayachandran A, Layton CJ, Steel JC. Seek and destroy: targeted adeno-associated viruses for gene delivery to hepatocellular carcinoma. Drug Deliv. 2017;24:289–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Srivastava A. In vivo tissue-tropism of adeno-associated viral vectors. Curr Opin Virol. 2016;21:75–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hagedorn C, Kreppel F. Capsid engineering of adenovirus vectors: overcoming early vector-host interactions for therapy. Hum Gene Ther. 2017;28:820–32.

    Article  CAS  PubMed  Google Scholar 

  56. Colella P, Ronzitti G, Mingozzi F, Development C. Emerging issues in AAV-mediated in vivo gene therapy. Mol Ther Methods Clin Dev. 2018;8:87–104.

    Article  CAS  PubMed  Google Scholar 

  57. Naso MF, Tomkowicz B, Perry WL, Strohl WR. Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs 2017;31:317–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Xie Q, Lerch TF, Meyer NL, Chapman MS. Structure-function analysis of receptor-binding in adeno-associated virus serotype 6 (AAV-6). Virology 2011;420:10–9.

    Article  CAS  PubMed  Google Scholar 

  59. Huang LY, Patel A, Ng R, Miller EB, Halder S, McKenna R, et al. Characterization of the adeno-associated virus 1 and 6 sialic acid binding site. J Virol. 2016;90:5219–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dane AP, Wowro SJ, Cunningham SC, Alexander IE. Comparison of gene transfer to the murine liver following intraperitoneal and intraportal delivery of hepatotropic AAV pseudo-serotypes. Gene Ther. 2013;20:460–4.

    Article  CAS  PubMed  Google Scholar 

  61. Büning H, Srivastava A. Capsid modifications for targeting and improving the efficacy of AAV vectors. Mol Ther Methods Clin Dev. 2019;12:248–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Zhong L, Li B, Jayandharan G, Mah CS, Govindasamy L, Agbandje-McKenna M, et al. Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression. Virology 2008;381:194–202.

    Article  CAS  PubMed  Google Scholar 

  63. Sen D, Gadkari RA, Sudha G, Gabriel N, Kumar YS, Selot R, et al. Targeted modifications in adeno-associated virus serotype 8 capsid improves its hepatic gene transfer efficiency in vivo. Hum Gene Ther Methods. 2013;24:104–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lochrie MA, Tatsuno GP, Christie B, McDonnell JW, Zhou S, Surosky R, et al. Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. J Virol. 2006;80:821–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, Buonaguro L. Antigen-specific vaccines for cancer treatment. Hum Vaccin Immunother. 2014;10:3332–46.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Grifman M, Trepel M, Speece P, Gilbert LB, Arap W, Pasqualini R, et al. Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. Mol Ther. 2001;3:964–75.

    Article  CAS  PubMed  Google Scholar 

  67. Alday-Parejo B, Stupp R, Rüegg C. Are integrins still practicable targets for anti-cancer therapy? Cancers 2019;11:978.

    Article  CAS  PubMed Central  Google Scholar 

  68. Sayroo R, Nolasco D, Yin Z, Colon-Cortes Y, Pandya M, Ling C, et al. Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells. Gene Ther. 2016;23:18–25.

    Article  CAS  PubMed  Google Scholar 

  69. Munch RC, Muth A, Muik A, Friedel T, Schmatz J, Dreier B, et al. Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors. Nat Commun. 2015;6:6246.

    Article  PubMed  CAS  Google Scholar 

  70. Munch RC, Janicki H, Volker I, Rasbach A, Hallek M, Buning H, et al. Displaying high-affinity ligands on adeno-associated viral vectors enables tumor cell-specific and safe gene transfer. Mol Ther. 2013;21:109–18.

    Article  PubMed  CAS  Google Scholar 

  71. Khan N, Bammidi S, Jayandharan GR. A CD33 antigen-targeted AAV6 vector expressing an inducible caspase-9 suicide gene is therapeutic in a xenotransplantation model of acute myeloid leukemia. Bioconjug Chem. 2019;30:2404–16.

    Article  CAS  PubMed  Google Scholar 

  72. Liu Y, Fang Y, Zhou Y, Zandi E, Lee CL, Joo KI, et al. Site-specific modification of adeno-associated viruses via a genetically engineered aldehyde tag. Small 2013;9:421–9.

    Article  CAS  PubMed  Google Scholar 

  73. Kelemen RE, Mukherjee R, Cao X, Erickson SB, Zheng Y, Chatterjee A. A precise chemical strategy to alter the receptor specificity of the adeno-associated virus. Angew Chem Int Ed Engl. 2016;55:10645–9.

    Article  CAS  PubMed  Google Scholar 

  74. Chandran JS, Sharp PS, Karyka E, Aves-Cruzeiro J, Coldicott I, Castelli L, et al. Site specific modification of adeno-associated virus enables both fluorescent imaging of viral particles and characterization of the capsid interactome. Sci Rep. 2017;7:14766.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Asuri P, Bartel MA, Vazin T, Jang JH, Wong TB, Schaffer DV. Directed evolution of adeno-associated virus for enhanced gene delivery and gene targeting in human pluripotent stem cells. Mol Ther. 2012;20:329–38.

    Article  CAS  PubMed  Google Scholar 

  76. Maheshri N, Koerber JT, Kaspar BK, Schaffer DV. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat Biotechnol. 2006;24:198–204.

    Article  CAS  PubMed  Google Scholar 

  77. Michelfelder S, Lee MK, deLima-Hahn E, Wilmes T, Kaul F, Muller O, et al. Vectors selected from adeno-associated viral display peptide libraries for leukemia cell-targeted cytotoxic gene therapy. Exp Hematol. 2007;35:1766–76.

    Article  CAS  PubMed  Google Scholar 

  78. Varadi K, Michelfelder S, Korff T, Hecker M, Trepel M, Katus HA, et al. Novel random peptide libraries displayed on AAV serotype 9 for selection of endothelial cell-directed gene transfer vectors. Gene Ther. 2012;19:800–9.

    Article  CAS  PubMed  Google Scholar 

  79. Dalkara D, Byrne LC, Klimczak RR, Visel M, Yin L, Merigan WH, et al. In vivo–directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous. Sci Transl Med. 2013;5:189ra76.

    Article  PubMed  CAS  Google Scholar 

  80. Wooley DP, Sharma P, Weinstein JR, Kotha Lakshmi Narayan P, Schaffer DV, Excoffon K. A directed evolution approach to select for novel adeno-associated virus capsids on an HIV-1 producer T cell line. J Virol Methods. 2017;250:47–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Davidsson M, Wang G, Aldrin-Kirk P, Cardoso T, Nolbrant S, Hartnor M, et al. A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism. Proc Natl Acad Sci USA. 2019;116:27053.

    Article  CAS  PubMed Central  Google Scholar 

  82. Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N. Engl J Med. 2008;358:2231–9.

    Article  CAS  PubMed  Google Scholar 

  83. Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl J Med. 2011;365:2357–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gillet J-P, Macadangdang B, Fathke RL, Gottesman MM, Kimchi-Sarfaty C. The development of gene therapy: from monogenic recessive disorders to complex diseases such as cancer. In: Walther W, Stein US, editors. Gene Therapy of Cancer. New York: Humana Press; 2009. p. 5–54.

  85. Ledford H. Cancer-fighting viruses win approval. Nature 2015;526:622–3.

    Article  CAS  PubMed  Google Scholar 

  86. Sun W, Shi Q, Zhang H, Yang K, Ke Y, Wang Y, et al. Advances in the techniques and methodologies of cancer gene therapy. Discov Med. 2019;27:45–55.

    CAS  PubMed  Google Scholar 

  87. Wirth T, Yla-Herttuala S. Gene therapy used in cancer treatment. Biomedicines 2014;2:149–62.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wang J, Lu XX, Chen DZ, Li SF, Zhang LS. Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer. World J Gastroenterol. 2004;10:400–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Rainov NG. A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther. 2000;11:2389–401.

    Article  CAS  PubMed  Google Scholar 

  90. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl J Med. 2011;365:1673–83.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Ramos CA, Asgari Z, Liu E, Yvon E, Heslop HE, Rooney CM, et al. An inducible caspase 9 suicide gene to improve the safety of mesenchymal stromal cell therapies. Stem Cells. 2010;28:1107–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bourgine P, Le Magnen C, Pigeot S, Geurts J, Scherberich A, Martin I. Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival. Stem Cell Res. 2014;12:584–98.

    Article  CAS  PubMed  Google Scholar 

  93. Rossignoli F, Grisendi G, Spano C, Golinelli G, Recchia A, Rovesti G, et al. Inducible Caspase9-mediated suicide gene for MSC-based cancer gene therapy. Cancer Gene Ther. 2019;26:11–6.

    Article  CAS  PubMed  Google Scholar 

  94. Khan N, Bammidi S, Chattopadhyay S, Jayandharan GR. Combination suicide gene delivery with an adeno-associated virus vector encoding inducible caspase-9 and a chemical inducer of dimerization is effective in a xenotransplantation model of hepatocellular carcinoma. Bioconjug Chem. 2019;30:1754–62.

    Article  CAS  PubMed  Google Scholar 

  95. Al-Husein B, Abdalla M, Trepte M, Deremer DL, Somanath PR. Antiangiogenic therapy for cancer: an update. Pharmacotherapy 2012;32:1095–111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl J Med. 1971;285:1182–6.

    Article  CAS  PubMed  Google Scholar 

  97. Ashrafi S, Shapouri R, Shirkhani A, Mahdavi M. Anti-tumor effects of propranolol: Adjuvant activity on a transplanted murine breast cancer model. Biomed Pharmacother. 2018;104:45–51.

    Article  CAS  PubMed  Google Scholar 

  98. Cicchelero L, Denies S, Haers H, Vanderperren K, Stock E, Van Brantegem L, et al. Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer. Vet Comp Oncol. 2017;15:1187–205.

    Article  CAS  PubMed  Google Scholar 

  99. Rajabi M, Mousa SA. The role of angiogenesis in cancer treatment. Biomedicines 2017;5:34.

    Article  PubMed Central  CAS  Google Scholar 

  100. Daud A, Takamura KT, Diep T, Heller R, Pierce RH. Long-term overall survival from a phase I trial using intratumoral plasmid interleukin-12 with electroporation in patients with melanoma. J Transl Med. 2015;13:O3.

    Article  PubMed Central  Google Scholar 

  101. Poutou J, Bunuales M, Gonzalez-Aparicio M, Garcia-Aragoncillo E, Quetglas JI, Casado R, et al. Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model. Gene Ther. 2015;22:696–706.

    Article  CAS  PubMed  Google Scholar 

  102. Koneru M, O’Cearbhaill R, Pendharkar S, Spriggs DR, Brentjens RJ. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16 ecto directed chimeric antigen receptors for recurrent ovarian cancer. J Transl Med. 2015;13:102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Kramer MG, Masner M, Casales E, Moreno M, Smerdou C, Chabalgoity JA. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice. BMC Cancer. 2015;15:1–15.

    Article  CAS  Google Scholar 

  104. Li T, Kang G, Wang T, Huang H. Tumor angiogenesis and anti-angiogenic gene therapy for cancer. Oncol Lett. 2018;16:687–702.

    PubMed  PubMed Central  Google Scholar 

  105. Chen X, Chen S, Pei N, Mao Y, Wang S, Yan R, et al. AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo. Oncotarget 2017;8:354.

    Article  PubMed  Google Scholar 

  106. Sun E, Han R, Lu B. Gene therapy of renal cancer using recombinant adeno‑associated virus encoding human endostatin. Oncol Lett. 2018;16:2789–96.

    PubMed  PubMed Central  Google Scholar 

  107. Shen Z, Yao C, Wang Z, Yue L, Fang Z, Yao H, et al. Vastatin, an endogenous antiangiogenesis polypeptide that is lost in hepatocellular carcinoma, effectively inhibits tumor metastasis. Mol Ther 2016;24:1358–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Rak B, Mehlich D, Garbicz F, Domosud Z, Paskal W, Marczewska JM, et al. Post-transcriptional regulation of MMP16 and TIMP2 expression via miR-382, miR-410 and miR-200b in endometrial cancer. Cancer Genom Proteom 2017;14:389–401.

    CAS  Google Scholar 

  109. Tan W, Liu B, Qu S, Liang G, Luo W, Gong C. MicroRNAs and cancer: Key paradigms in molecular therapy. Oncol Lett. 2018;15:2735–42.

    PubMed  Google Scholar 

  110. Wu Y, Song Y, Xiong Y, Wang X, Xu K, Han B, et al. MicroRNA-21 (Mir-21) promotes cell growth and invasion by repressing tumor suppressor PTEN in colorectal cancer. Cell Physiol Biochem. 2017;43:945–58.

    Article  CAS  PubMed  Google Scholar 

  111. Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, et al. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA. 2008;105:2889–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Shuang T, Shi C, Chang S, Wang M, Bai CH. Downregulation of miR-17~19 expression increase paclitaxel sensitivity in human ovarian carcinoma SKOV3-TR30 cells via BIM instead of PTEN. Int J Mol Sci. 2013;14:3802–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Osada H, Takahashi T. let-7 and miR-17-92: small-sized major players in lung cancer development. Cancer Sci. 2011;102:9–17.

    Article  CAS  PubMed  Google Scholar 

  114. Labi V, Schoeler K, Melamed D. miR-17∼ 92 in lymphocyte development and lymphomagenesis. Cancer Lett. 2019;446:73–80.

    Article  CAS  PubMed  Google Scholar 

  115. Zhou X, Zhang CZ, Lu SX, Chen GG, Li LZ, Liu LL, et al. miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma. Oncogene 2015;34:965–77.

    Article  CAS  PubMed  Google Scholar 

  116. Beg MS, Brenner AJ, Sachdev J, Borad M, Kang YK, Stoudemire J, et al. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest N. Drugs. 2017;35:180–8.

    Article  CAS  Google Scholar 

  117. Shi Y, Liu C, Liu X, Tang DG, Wang J. The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44 hi stem-like NSCLC cells. PLoS ONE. 2014;9:e90022.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010;327:198–201.

    Article  CAS  PubMed  Google Scholar 

  119. Li G, Fang J, Wang Y, Wang H, Sun CC. MiRNA-based therapeutic strategy in lung cancer. Curr Pharm Des. 2017;23:6011–8.

    Article  CAS  Google Scholar 

  120. Goradel NH, Mohammadi N, Haghi‐Aminjan H, Farhood B, Negahdari B, Sahebkar A. Regulation of tumor angiogenesis by microRNAs: State of the art. J Cell Physiol. 2019;234:1099–110.

    Article  CAS  PubMed  Google Scholar 

  121. Yang C, Ma X, Guan G, Liu H, Yang Y, Niu Q, et al. MicroRNA-766 promotes cancer progression by targeting NR3C2 in hepatocellular carcinoma. FASEB J. 2019;33:1456–67.

    Article  CAS  PubMed  Google Scholar 

  122. Rupaimoole R, Calin GA, Lopez-Berestein G, Sood AK. miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 2016;6:235–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Gharpure KM, Nagaraja AS, Armaiz-pena GN, Zand B, Dalton HJ, Filant J, et al. Hypoxia mediated downregulation of miRNA biogenesis promotes tumor progression. Nat Commun. 2015;5:1–13.

    Google Scholar 

  124. Uppendahl LD, Dahl CM, Miller JS, Felices M, Geller MA. Natural killer cell-based immunotherapy in gynecologic malignancy: a Review. Front Immunol. 2017;8:1825.

    Article  PubMed  CAS  Google Scholar 

  125. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13:273–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Papaioannou NE, Beniata OV, Vitsos P, Tsitsilonis O, Samara P. Harnessing the immune system to improve cancer therapy. Ann Transl Med. 2016;4:261.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12:509–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Zamora AE, Crawford JC, Thomas PG. Hitting the target: how T cells detect and eliminate tumors. J Immunol. 2018;200:392–9.

    Article  CAS  PubMed  Google Scholar 

  129. Brown CE, Mackall CL. CAR T cell therapy: inroads to response and resistance. Nat Rev Immunol. 2019;19:73–4.

    Article  CAS  PubMed  Google Scholar 

  130. Xu D, Jin G, Chai D, Zhou X, Gu W, Chong Y, et al. The development of CAR design for tumor CAR-T cell therapy. Oncotarget 2018;9:13991–4004.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3:388–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015;385:517–28.

    Article  CAS  PubMed  Google Scholar 

  133. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl J Med. 2018;378:439–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N. Engl J Med. 2019;380:45–56.

    Article  CAS  PubMed  Google Scholar 

  135. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-Cell lymphoma. N. Engl J Med. 2017;377:2531–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Jiang Z, Jiang X, Chen S, Lai Y, Wei X, Li B, et al. Anti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma. Front Immunol. 2016;7:690.

    PubMed  CAS  Google Scholar 

  137. Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 2015;161:205–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Mehta RS, Rezvani K. Chimeric antigen receptor expressing natural killer cells for the immunotherapy of cancer. Front Immunol. 2018;9:283.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Le TP, Thai TH. The state of cellular adoptive immunotherapy for neuroblastoma and other pediatric solid tumors. Front Immunol. 2017;8:1640.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Tian X, Wei F, Wang L, Yu W, Zhang N, Zhang X, et al. Herceptin enhances the antitumor effect of natural killer cells on breast cancer cells expressing human epidermal growth factor receptor-2. Front Immunol. 2017;8:1426.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Hou B, Tang Y, Li W, Zeng Q, Chang D. Efficiency of CAR-T therapy for treatment of solid tumor in clinical trials: A meta-analysis. Dis Markers. 2019;2019:3425291.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Zhang WW, Li L, Li D, Liu J, Li X, Li W, et al. The first approved gene therapy product for cancer Ad-p53 (Gendicine): 12 years in the clinic. Hum Gene Ther. 2018;29:160–79.

    Article  CAS  PubMed  Google Scholar 

  143. Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Sci. 2016;107:1373–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Zhang W, Wang F, Hu X, Liang J, Liu B, Guan Q, et al. Inhibition of colorectal cancer liver metastasis in BALB/c mice following intratumoral injection of oncolytic herpes simplex virus type 2 for the induction of specific antitumor immunity. Oncol Lett. 2019;17:815–22.

    CAS  PubMed  Google Scholar 

  145. Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 2014;346:1258096.

    Article  PubMed  CAS  Google Scholar 

  146. Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 2014;157:1262–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. RNA-guided human genome engineering via Cas9. Science 2013;339:823–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Martinez-Lage M, Puig-Serra P, Menendez P, Torres-Ruiz R, Rodriguez-Perales S. CRISPR/Cas9 for cancer therapy: Hopes and challenges. Biomedicines 2018;6:1–13.

    Article  CAS  Google Scholar 

  149. Zhao G, Wang Q, Gu Q, Qiang W, Wei JJ, Dong P, et al. Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells. Oncotarget 2017;8:94666–80.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Huo W, Zhao G, Yin J, Ouyang X, Wang Y, Yang C, et al. Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells. J Cancer. 2017;8:57–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Tang KJ, Constanzo JD, Venkateswaran N, Melegari M, Ilcheva M, Morales JC, et al. Focal adhesion kinase regulates the DNA damage response and its inhibition radiosensitizes mutant KRAS lung cancer. Clin Cancer Res. 2016;22:5851–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Mou H, Moore J, Malonia SK, Li Y, Ozata DM, Hough S, et al. Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis. Proc Natl Acad Sci USA. 2017;114:3648–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Koo T, Yoon AR, Cho HY, Bae S, Yun CO, Kim JS. Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression. Nucleic Acids Res. 2017;45:7897–908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Shen F, Zhang Y, Jernigan DL, Feng X, Yan J, Garcia FU, et al. Novel small-molecule CX3CR1 antagonist impairs metastatic seeding and colonization of breast cancer cells. Mol Cancer Res. 2016;14:518–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Jin K, Pandey NB, Popel AS. Crosstalk between stromal components and tumor cells of TNBC via secreted factors enhances tumor growth and metastasis. Oncotarget 2017;8:60210–22.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Wang L, Minchin RF, Butcher NJ. Arylamine N-acetyltransferase 1 protects against reactive oxygen species during glucose starvation: Role in the regulation of p53 stability. PLoS ONE. 2018;13:e0193560.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Lal S, Cheung EC, Zarei M, Preet R, Chand SN, Mambelli-Lisboa NC, et al. CRISPR knockout of the HuR gene causes a xenograft lethal phenotype. Mol Cancer Res. 2017;15:696–707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Yoshida K, Toden S, Weng W, Shigeyasu K, Miyoshi J, Turner J, et al. SNORA21-An oncogenic small nucleolar RNA, with a prognostic biomarker potential in human colorectal cancer. EBioMedicine 2017;22:68–77.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Maerken M, MacEwan D, Harper N, Slupsky JR, Linley A. Gene editing of BTK in acute myeloid leukaemia using CRISPR-Cas9. Blood. 2018;132:3952.

    Article  Google Scholar 

  160. Ercolano G, De Cicco P, Rubino V, Terrazzano G, Ruggiero G, Carriero R, et al. Knockdown of PTGS2 by CRISPR/CAS9 system designates a new potential gene target for melanoma treatment. Front Pharm. 2019;10:1456.

    Article  CAS  Google Scholar 

  161. Wang X, Zhang W, Ding Y, Guo X, Yuan Y, Li D. CRISPR/Cas9-mediated genome engineering of CXCR4 decreases the malignancy of hepatocellular carcinoma cells in vitro and in vivo. Oncol Rep. 2017;37:3565–71.

    Article  CAS  PubMed  Google Scholar 

  162. He J, Zhang W, Li A, Chen F, Luo R. Knockout of NCOA5 impairs proliferation and migration of hepatocellular carcinoma cells by suppressing epithelial-to-mesenchymal transition. Biochem Biophys Res Commun. 2018;500:177–83.

    Article  CAS  PubMed  Google Scholar 

  163. Zhu B, Chen S, Hu X, Jin X, Le Y, Cao L, et al. Knockout of the Nogo-B gene attenuates tumor growth and metastasis in hepatocellular carcinoma. Neoplasia 2017;19:583–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Zhan T, Rindtorff N, Betge J, Ebert MP, Boutros M. CRISPR/Cas9 for cancer research and therapy. Semin Cancer Biol. 2019;55:106–19.

    Article  CAS  PubMed  Google Scholar 

  165. Valletta S, Dolatshad H, Bartenstein M, Yip BH, Bello E, Gordon S, et al. ASXL1 mutation correction by CRISPR/Cas9 restores gene function in leukemia cells and increases survival in mouse xenografts. Oncotarget 2015;6:44061–71.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Weber J, Öllinger R, Friedrich M, Ehmer U, Barenboim M, Steiger K, et al. CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice. Proc Natl Acad Sci USA. 2015;112:13982–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Yoshiba T, Saga Y, Urabe M, Uchibori R, Matsubara S, Fujiwara H, et al. CRISPR/Cas9-mediated cervical cancer treatment targeting human papillomavirus E6. Oncol Lett. 2019;17:2197–206.

    CAS  PubMed  Google Scholar 

  168. Ahmad G, Amiji M. Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery. Drug Discov Today. 2018;23:519–33.

    Article  CAS  PubMed  Google Scholar 

  169. Scott A. How CRISPR is transforming drug discovery. Nature 2018;555:S10–1.

    Article  CAS  PubMed  Google Scholar 

  170. Neggers JE, Vercruysse T, Jacquemyn M, Vanstreels E, Baloglu E, Shacham S, et al. Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by CRISPR/Cas9 genome editing. Chem Biol. 2015;22:107–16.

    Article  CAS  PubMed  Google Scholar 

  171. Fang Y, Fullwood MJ. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genom Proteom Bioinf. 2016;14:42–54.

    Article  Google Scholar 

  172. Jiang M-C, Ni J-J, Cui W-Y, Wang B-Y, Zhuo W. Emerging roles of lncRNA in cancer and therapeutic opportunities. Am J Cancer Res. 2019;9:1354–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Adriaens C, Standaert L, Barra J, Latil M, Verfaillie A, Kalev P, et al. p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nat Med. 2016;22:861–8.

    Article  CAS  PubMed  Google Scholar 

  174. Mendell JT. Targeting a long noncoding RNA in breast cancer. N. Engl J Med. 2016;374:2287–9.

    Article  PubMed  Google Scholar 

  175. Zhao ZJ, Shen J. Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol. 2017;14:514–21.

    Article  PubMed  Google Scholar 

  176. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013;495:384–8.

    Article  CAS  PubMed  Google Scholar 

  177. Yu J, Xu Q-G, Wang Z-G, Yang Y, Zhang L, Ma J-Z, et al. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol. 2018;68:1214–27.

    Article  CAS  PubMed  Google Scholar 

  178. Wang S, Zhang X, Li Z, Wang W, Li B, Huang X, et al. Circular RNA profile identifies circOSBPL10 as an oncogenic factor and prognostic marker in gastric cancer. Oncogene 2019;38:6985–7001.

    Article  CAS  PubMed  Google Scholar 

  179. Chen S, Li T, Zhao Q, Xiao B, Guo J. Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer. Clin Chim Acta. 2017;466:167–71.

    Article  CAS  PubMed  Google Scholar 

  180. Kucinska M, Murias M, Nowak-Sliwinska P. Beyond mouse cancer models: Three-dimensional human-relevant in vitro and non-mammalian in vivo models for photodynamic therapy. Mutat Res Rev Mutat Res. 2017;773:242–62.

    Article  CAS  PubMed  Google Scholar 

  181. Ueda Y, Kawamoto K, Konno M, Noguchi K, Kaifuchi S, Satoh T, et al. Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice. Oncotarget 2019;10:5412–8.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Hason M, Bartůnĕk P. Zebrafish models of cancer-new insights on modeling human cancer in a non-mammalian vertebrate. Genes 2019;10:1–30.

    Article  CAS  Google Scholar 

  183. Khan N, Mahajan NK, Sinha P, Jayandharan GR. An efficient method to generate xenograft tumor models of acute myeloid leukemia and hepatocellular carcinoma in adult zebrafish. Blood Cells Mol Dis. 2019;75:48–55.

    Article  CAS  PubMed  Google Scholar 

  184. Sonoshita M, Cagan RL. Modeling human cancers in Drosophila. In: Sonoshita M, Cagan RL, editors. Modeling human cancers in Drosophila. Current topics in developmental biology.Vol. 121, Academic Press; 2017. p. 287–309.

  185. Olson B, Li Y, Lin Y, Liu ET, Patnaik A. Mouse models for cancer immunotherapy research. Cancer Discov. 2018;8:1358–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Siddiqui SS, Loganathan S, Krishnaswamy S, Faoro L, Jagadeeswaran R, Salgia RC. elegans as a model organism for in vivo screening in cancer: effects of human c-Met in lung cancer affect C. elegans vulva phenotypes. Cancer Biol Ther. 2008;7:856–63.

    Article  CAS  PubMed  Google Scholar 

  187. Henarejos-Escudero P, Hernandez-Garcia S, Guerrero-Rubio MA, Garcia-Carmona F, Gandia-Herrero F. Antitumoral drug potential of tryptophan-betaxanthin and related plant betalains in the Caenorhabditis elegans tumoral model. Antioxidants 2020;9:646.

    Article  CAS  PubMed Central  Google Scholar 

  188. Meier B, Volkova NV, Hong Y, Schofield P, Campbell PJ, Gerstung M, et al. Mutational signatures of DNA mismatch repair deficiency in C. elegans and human cancers. Genome Res. 2018;28:666–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Motta-Mena LB, Reade A, Mallory MJ, Glantz S, Weiner OD, Lynch KW, et al. An optogenetic gene expression system with rapid activation and deactivation kinetics. Nat Chem Biol. 2014;10:196–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Pandey UB, Nichols CD. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharm Rev. 2011;63:411–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Schook LB, Collares TV, Hu W, Liang Y, Rodrigues FM, Rund LA, et al. A Genetic porcine model of cancer. PLoS ONE. 2015;10:e0128864.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Lampreht Tratar U, Horvat S, Cemazar M. Transgenic mouse models in cancer research. Front Oncol. 2018;8:268.

    Article  PubMed  PubMed Central  Google Scholar 

  193. Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol. 2020;13:4.

    Article  PubMed  PubMed Central  Google Scholar 

  194. Suarez CD, Littlepage LE. Patient-derived tumor xenograft models of breast cancer. In: Cao J, editor. Breast Cancer. New York, Humana Press; 2016. p. 211–23.

  195. Inoue T, Terada N, Kobayashi T, Ogawa O. Patient-derived xenografts as in vivo models for research in urological malignancies. Nat Rev Urol. 2017;14:267–83.

    Article  PubMed  Google Scholar 

  196. Lai Y, Wei X, Lin S, Qin L, Cheng L, Li P, et al. Current status and perspectives of patient-derived xenograft models in cancer research. J Hematol Oncol. 2017;10:1–14.

    Article  CAS  Google Scholar 

  197. Wang M, Yao LC, Cheng M, Cai D, Martinek J, Pan CX, et al. Humanized mice in studying efficacy and mechanisms of PD‐1‐targeted cancer immunotherapy. FASEB J. 2018;32:1537–49.

    Article  CAS  PubMed  Google Scholar 

  198. Nirenberg MW. Will society be prepared? Science 1967;157:633.

    Article  CAS  PubMed  Google Scholar 

  199. Germano IM, Fable J, Gultekin SH, Silvers A. Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. J Neuro-Oncol. 2003;65:279–89.

    Article  Google Scholar 

  200. Kreitman RJ, Squires DR, Stetler-Stevenson M, Noel P, FitzGerald DJ, Wilson WH, et al. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. 2005;23:6719–29.

    Article  CAS  PubMed  Google Scholar 

  201. Borthakur G, Rosenblum MG, Talpaz M, Daver N, Ravandi F, Faderl S, et al. Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced myeloid malignancies. Haematologica 2013;98:217–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Kanazawa T, Mizukami H, Okada T, Hanazono Y, Kume A, Nishino H, et al. Suicide gene therapy using AAV-HSVtk/ganciclovir in combination with irradiation results in regression of human head and neck cancer xenografts in nude mice. Gene Ther. 2003;10:51–8.

    Article  CAS  PubMed  Google Scholar 

  203. Brown HK, Schiavone K, Tazzyman S, Heymann D, Chico TJ. Zebrafish xenograft models of cancer and metastasis for drug discovery. Expert Opin Drug Discov. 2017;12:379–89.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Ms. Pratiksha Sarangi and Mr. Shamshul Huda, Molecular Genetics and Therapeutics laboratory, BSBE, IIT-Kanpur for review of the manuscript.

Funding

This work was supported by a Nanomission grant SR/NM/NS-1084/2016 and an in-part support from the Wellcome Trust DBT India Alliance Senior fellowship (IA/S/16/1/502355) and ASPIRE research award from Pfizer, Inc. USA (#5359919) awarded to GRJ. VS and NK were supported by a Ph.D. fellowship (MHRD grant to IIT-Kanpur).

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  1. Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, UP, India

    Vijayata Singh, Nusrat Khan & Giridhara R. Jayandharan

  2. The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology, Kanpur, UP, India

    Giridhara R. Jayandharan

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Correspondence to Giridhara R. Jayandharan.

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Singh, V., Khan, N. & Jayandharan, G.R. Vector engineering, strategies and targets in cancer gene therapy. Cancer Gene Ther 29, 402–417 (2022). https://doi.org/10.1038/s41417-021-00331-7

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