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Suicide gene strategies applied in ovarian cancer studies

Cancer Gene Therapy volume 30, pages 812–821 (2023)Cite this article

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Abstract

Ovarian cancer represents the most lethal gynecological malignancy among women in developed countries. Despite the recent innovations, the improvements in the 5-year survival rate have been insufficient and the management of this disease still remains a challenge. The fact that the majority of patients experience recurrent or resistant disease have substantiated the necessity of an innovative treatment. Among various strategies investigated, the recent strides made in gene delivery techniques have made gene therapy, including suicide gene strategies, a potential alternative for treating ovarian cancer. Various suicide gene candidates, which are capable of promoting cancer cell apoptosis directly after its entry or indirectly by prodrug administration, can be separated into three systems using enzyme-coding, toxin or pro-apoptotic genes. With this review, we aim to provide an overview of different suicide genes depending on therapeutic strategies, the vectors used to deliver these transgenes specifically to malignant cells, and the combined treatments of these genes with various therapeutic regimens.

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Fig. 1: Overview of suicide gene strategies investigated in OC.
Fig. 2: Prodrugs conversion by enzyme into cytotoxic compounds.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  2. Brett MR, Jennifer BP, Thomas AS, Brett MR, Jennifer BP, Thomas AS. Epidemiology of ovarian cancer: a review. Cancer Biol Med. 2017;14:9–32.

    Article  Google Scholar 

  3. Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385:977–1010.

    Article  PubMed  Google Scholar 

  4. Kuroki L, Guntupalli SR. Treatment of epithelial ovarian cancer. BMJ. 2020;371:m3773.

    Article  PubMed  Google Scholar 

  5. Guan LY, Lu Y. New developments in molecular targeted therapy of ovarian cancer. Discov Med. 2018;26:219–29.

    PubMed  Google Scholar 

  6. Lord CJ, Ashworth A. Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med. 2013;19:1381–8.

    Article  CAS  PubMed  Google Scholar 

  7. Itatani Y, Kawada K, Yamamoto T, Sakai Y. Resistance to Anti-Angiogenic Therapy in Cancer—Alterations to Anti-VEGF Pathway. Int J Mol Sci. 2018;19:1232.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Grunewald T, Ledermann JA. Targeted Therapies for Ovarian Cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:139–52.

    Article  PubMed  Google Scholar 

  9. Malecki M, Dahlke J, Haig M, Wohlwend L, Malecki R. Eradication of Human Ovarian Cancer Cells by Transgenic Expression of Recombinant DNASE1, DNASE1L3, DNASE2, and DFFB Controlled by EGFR Promoter: Novel Strategy for Targeted Therapy of Cancer. J Genet Syndr Gene Ther. 2013;4:152.

    PubMed  PubMed Central  Google Scholar 

  10. Song JS, Kim HP, Yoon WS, Lee KW, Kim MH, Kim KT, et al. Adenovirus-mediated suicide gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter induced apoptosis of ovarian cancer cell line. Biosci Biotechnol Biochem. 2003;67:2344–50.

    Article  CAS  PubMed  Google Scholar 

  11. Tait DL, Obermiller PS, Jensen RA, Holt JT. Ovarian cancer gene therapy. Hematol Oncol Clin North Am. 1998;12:539–52.

    Article  CAS  PubMed  Google Scholar 

  12. Áyen Á, Jiménez Martínez Y, Marchal J, Boulaiz H. Recent Progress in Gene Therapy for Ovarian Cancer. IJMS. 2018;19:1930.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hallaj-Nezhadi S, Dass CR, Lotfipour F. Intraperitoneal delivery of nanoparticles for cancer gene therapy. Future Oncol. 2013;9:59–68.

    Article  CAS  PubMed  Google Scholar 

  14. Navarro SA, Carrillo E, Griñán-Lisón C, Martín A, Perán M, Marchal JA, et al. Cancer suicide gene therapy: a patent review. Expert Opin Ther Pat. 2016;26:1095–104.

    Article  CAS  PubMed  Google Scholar 

  15. Duarte S, Carle G, Faneca H, Lima MCP, de, Pierrefite-Carle V. Suicide gene therapy in cancer: Where do we stand now? Cancer Lett. 2012;324:160–70.

    Article  CAS  PubMed  Google Scholar 

  16. Düzgüneş N. Origins of Suicide Gene Therapy. In: Düzgüneş N, editor. Suicide Gene Therapy. New York, NY: Springer New York; 2019. p. 1–9. (Methods in Molecular Biology; vol. 1895). Accessed 2022 Jan 25. http://link.springer.com/10.1007/978-1-4939-8922-5_1

  17. Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 1986;46:5276–81.

    CAS  PubMed  Google Scholar 

  18. David S, Carmoy N, Resnier P, Denis C, Misery L, Pitard B, et al. In vivo imaging of DNA lipid nanocapsules after systemic administration in a melanoma mouse model. Int J Pharm. 2012;423:108–15.

    Article  CAS  PubMed  Google Scholar 

  19. Balfour HH. Antiviral drugs. N. Engl J Med. 1999;340:1255–68.

    Article  CAS  PubMed  Google Scholar 

  20. Matthews T, Boehme R. Antiviral activity and mechanism of action of ganciclovir. Rev Infect Dis. 1988;10:S490–494.

    Article  CAS  PubMed  Google Scholar 

  21. Shirley JL, Jong YP, de, Terhorst C, Herzog RW. Immune Responses to Viral Gene Therapy Vectors. Mol Ther. 2020;28:709–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tong X, Engehausen DG, Freund CT, Agoulnik I, Oehler MK, Kim TE, et al. Comparison of long-term survival of cytomegalovirus promotre versus Rous Sarcoma virus promoter-driven thymidine kinase gene therapy in nude mice bearing human ovarian cancer. Hybridoma. 1999;18:93–7.

    Article  CAS  PubMed  Google Scholar 

  23. Pruller J, Hofer I, Ganassi M, Heher P, Ma MT, Zammit PS. Correction: A human Myogenin promoter modified to be highly active in alveolar rhabdomyosarcoma drives an effective suicide gene therapy. Cancer Gene Ther. 2021;28:544–544.

    Article  CAS  PubMed  Google Scholar 

  24. Wang Y, Xu HX, Lu MD, Tang Q. Expression of thymidine kinase mediated by a novel non-viral delivery system under the control of vascular endothelial growth factor receptor 2 promoter selectively kills human umbilical vein endothelial cells. World J Gastroenterol. 2008;14:224–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mu X, Wang X, Wei Y, Wen C, Zhang Q, Xu C, et al. ApoE-modified liposomes mediate the antitumour effect of survivin promoter-driven HSVtk in hepatocellular carcinoma. Cancer Gene Ther. 2020;27:754–67.

    Article  CAS  PubMed  Google Scholar 

  26. Rawlinson JW, Vaden K, Hunsaker J, Miller DF, Nephew KP. Adenoviral-delivered HE4-HSV-tk sensitizes ovarian cancer cells to ganciclovir. Gene Ther Mol Biol. 2013;15:120–30.

    PubMed  PubMed Central  Google Scholar 

  27. Li Y, Zhao S, Zhang F, Jin G, Zhou Y, Li P, et al. Molecular imaging-monitored radiofrequency hyperthermia-enhanced intratumoral herpes simplex virus-thymidine kinase gene therapy for rat orthotopic ovarian cancer. Int J Hyperth. 2020;37:101–9.

    Article  CAS  Google Scholar 

  28. Hong S, Zhang P, Zhang H, Jia L, Qu X, Yang Q, et al. Enforced effect of tk-MCP-1 fusion gene in ovarian cancer. J Exp Clin Cancer Res. 2012;31:74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Montier T, Benvegnu T, Jaffrès PA, Yaouanc JJ, Lehn P. Progress in Cationic Lipid-Mediated Gene Transfection: A Series of Bio-Inspired Lipids as an Example. Curr Gene Ther. 2008;8:296–312.

    Article  CAS  PubMed  Google Scholar 

  30. Thomas C, Ehrhardt A, Kay M, Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4, 346-358. Nat Rev Genet. 2003;4:346–58.

    Article  CAS  PubMed  Google Scholar 

  31. Kang Y, Zhang X, Jiang W, Wu C, Chen C, Zheng Y, et al. Tumor-directed gene therapy in mice using a composite nonviral gene delivery system consisting of the piggyBac transposon and polyethylenimine. BMC Cancer. 2009;9:126.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Austin EA, Huber BE. A first step in the development of gene therapy for colorectal carcinoma: cloning, sequencing, and expression of Escherichia coli cytosine deaminase. Mol Pharm. 1993;43:380–7.

    CAS  Google Scholar 

  33. Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3:330–8.

    Article  CAS  PubMed  Google Scholar 

  34. Tiraby M, Cazaux C, Baron M, Drocourt D, Reynes JP, Tiraby G. Concomitant expression of E. coli cytosine deaminase and uracil phosphoribosyltransferase improves the cytotoxicity of 5-fluorocytosine. FEMS Microbiol Lett. 1998;167:41–9.

    Article  CAS  PubMed  Google Scholar 

  35. Akbulut H, Zhang L, Tang Y, Deisseroth A. Cytotoxic effect of replication-competent adenoviral vectors carrying L-plastin promoter regulated E1A and cytosine deaminase genes in cancers of the breast, ovary and colon. Cancer Gene Ther. 2003;10:388–95.

    Article  CAS  PubMed  Google Scholar 

  36. Bourbeau D, Lau CJ, Jaime J, Koty Z, Zehntner SP, Lavoie G, et al. Improvement of Antitumor Activity by Gene Amplification with a Replicating but Nondisseminating Adenovirus. Cancer Res. 2007;67:3387–95.

    Article  CAS  PubMed  Google Scholar 

  37. Wang Z, Cai L, Wang H. Gene therapy of adenovirus mediated CD::upp/5-FC directed by GSTP1 promoter in cisplatin-resistant ovarian cancer. Gynecol Oncol. 2005;96:643–50.

    Article  CAS  PubMed  Google Scholar 

  38. Lu S, Wang X, Xiao L, Cai L, Zhang Y, Wang H, et al. Gene therapy for ovarian cancer using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene directed by MDR1 promoter. Cancer Biol Ther. 2007;6:397–404.

    Article  CAS  PubMed  Google Scholar 

  39. Chalikonda S, Kivlen MH, O’Malley ME, Eric Dong XD, McCart JA, Gorry MC, et al. Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene. Cancer Gene Ther. 2008;15:115–25.

    Article  CAS  PubMed  Google Scholar 

  40. Hartkopf AD, Bossow S, Lampe J, Zimmermann M, Taran FA, Wallwiener D, et al. Enhanced killing of ovarian carcinoma using oncolytic measles vaccine virus armed with a yeast cytosine deaminase and uracil phosphoribosyltransferase. Gynecol Oncol. 2013;130:362–8.

    Article  CAS  PubMed  Google Scholar 

  41. Altanerova U, Jakubechova J, Benejova K, Priscakova P, Repiska V, Babelova A, et al. Intracellular prodrug gene therapy for cancer mediated by tumor cell suicide gene exosomes. Int J Cancer. 2021;148:128–39.

    Article  CAS  PubMed  Google Scholar 

  42. Song Y, Kong B, Ma D, Qu X, Jiang S. Procaspase-3 enhances the in vitro effect of cytosine deaminase-thymidine kinase disuicide gene therapy on human ovarian cancer. Int J Gynecol Cancer. 2006;16:156–64.

    Article  CAS  PubMed  Google Scholar 

  43. Sher YP, Chang CM, Juo CG, Chen CT, Hsu JL, Lin CY, et al. Targeted endostatin-cytosine deaminase fusion gene therapy plus 5-fluorocytosine suppresses ovarian tumor growth. Oncogene. 2013;32:1082–90.

    Article  CAS  PubMed  Google Scholar 

  44. Rodini CO, Gonçalves da Silva PB, Assoni AF, Carvalho VM, Okamoto OK. Mesenchymal stem cells enhance tumorigenic properties of human glioblastoma through independent cell-cell communication mechanisms. Oncotarget. 2018;9:24766–77.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med. 2013;19:998–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jiang J, Wei D, Sun L, Wang Y, Wu X, Li Y, et al. A preliminary study on the construction of double suicide gene delivery vectors by mesenchymal stem cells and the in vitro inhibitory effects on SKOV3 cells. Oncol Rep. 2014;31:781–7.

    Article  CAS  PubMed  Google Scholar 

  47. Bridgewater JA, Springer CJ, Knox RJ, Minton NP, Michael NP, Collins MK. Expression of the bacterial nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954. Eur J Cancer. 1995;31:2362–70.

    Article  Google Scholar 

  48. Bilsland AE, Anderson CJ, Fletcher-Monaghan AJ, McGregor F, Jeffry Evans TR, Ganly I, et al. Selective ablation of human cancer cells by telomerase-specific adenoviral suicide gene therapy vectors expressing bacterial nitroreductase. Oncogene. 2003;22:370–80.

    Article  CAS  PubMed  Google Scholar 

  49. Harvey TJ, Hennig IM, Shnyder SD, Cooper PA, Ingram N, Hall GD, et al. Adenovirus-mediated hypoxia-targeted gene therapy using HSV thymidine kinase and bacterial nitroreductase prodrug-activating genes in vitro and in vivo. Cancer Gene Ther. 2011;18:773–84.

    Article  CAS  PubMed  Google Scholar 

  50. Brown JM. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Mol Med Today. 2000;6:157–62.

    Article  CAS  PubMed  Google Scholar 

  51. McKeown SR. Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response. Br J Radio. 2014;87:20130676.

    Article  CAS  Google Scholar 

  52. Weedon SJ, Green NK, McNeish IA, Gilligan MG, Mautner V, Wrighton CJ, et al. Sensitisation of human carcinoma cells to the prodrug CB1954 by adenovirus vector-mediated expression of E. coli nitroreductase. Int J Cancer. 2000;86:848–54.

    Article  CAS  PubMed  Google Scholar 

  53. Grove JI, Lovering AL, Guise C, Race PR, Wrighton CJ, White SA, et al. Generation of Escherichia Coli Nitroreductase Mutants Conferring Improved Cell Sensitization to the Prodrug CB1954. Cancer Res. 2003;63:5532–7.

    CAS  PubMed  Google Scholar 

  54. Jaberipour M, Vass SO, Guise CP, Grove JI, Knox RJ, Hu L, et al. Testing double mutants of the enzyme nitroreductase for enhanced cell sensitisation to prodrugs: Effects of combining beneficial single mutations. Biochem Pharmacol. 2010;79:102–11.

    Article  CAS  PubMed  Google Scholar 

  55. Vass SO, Jarrom D, Wilson WR, Hyde EI, Searle PF. E. coli NfsA: an alternative nitroreductase for prodrug activation gene therapy in combination with CB1954. Br J Cancer. 2009;100:1903–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Oishi T, Ito M, Koizumi S, Horikawa M, Yamamoto T, Yamagishi S, et al. Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases. Mol Ther Methods Clin Dev 2022;26:253–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Preuß E, Treschow A, Newrzela S, Brücher D, Weber K, Felldin U, et al. TK.007: A Novel, Codon-Optimized HSVtk(A168H) Mutant for Suicide Gene Therapy. https://home.liebertpub.com/hum. Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA; 2010. Accessed 2022 Dec 12. https://www.liebertpub.com/doi/10.1089/hum.2009.042

  58. Palmer DH, Milner AE, Kerr DJ, Young LS. Mechanism of cell death induced by the novel enzyme-prodrug combination, nitroreductase/CB1954, and identification of synergism with 5-fluorouracil. Br J Cancer. 2003;89:944–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. White CL, Menghistu T, Twigger KR, Searle PF, Bhide SA, Vile RG, et al. Escherichia coli nitroreductase plus CB1954 enhances the effect of radiotherapy in vitro and in vivo. Gene Ther. 2008;15:424–33.

    Article  CAS  PubMed  Google Scholar 

  60. Nouri FS, Wang X, Hatefi A. Genetically engineered theranostic mesenchymal stem cells for the evaluation of the anticancer efficacy of enzyme/prodrug systems. J Control Release. 2015;200:179–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Parker WB, Allan PW, Shaddix SC, Rose LM, Speegle HF, Gillespie GY, et al. Metabolism and Metabolic Actions of 6-Methylpurine and 2-Fluoroadenine in Human Cells. Biochem Pharmacol. 1998;55:1673–81.

    Article  CAS  PubMed  Google Scholar 

  62. Hughes BW, King SA, Allan PW, Parker WB, Sorscher EJ. Cell to Cell Contact Is Not Required for Bystander Cell Killing by Escherichia coli Purine Nucleoside Phosphorylase *. J Biol Chem. 1998;273:2322–8.

    Article  CAS  PubMed  Google Scholar 

  63. Singh PP, Joshi S, Russell PJ, Nair S, Khatri A. Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer. BMC Cancer. 2011;11:368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gadi VK, Alexander SD, Kudlow JE, Allan P, Parker WB, Sorscher EJ. In vivo sensitization of ovarian tumors to chemotherapy by expression of E. coli purine nucleoside phosphorylase in a small fraction of cells. Gene Ther. 2000;7:1738–43.

    Article  CAS  PubMed  Google Scholar 

  65. Karjoo Z, Chen X, Hatefi A. Progress and problems with the use of suicide genes for targeted cancer therapy. Adv Drug Deliv Rev. 2016;99:113–28.

    Article  CAS  PubMed  Google Scholar 

  66. Bennett MJ, Eisenberg D. Refined structure of monomeric diphtheria toxin at 2.3 A resolution. Protein Sci. 1994;3:1464–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Huang YH, Zugates GT, Peng W, Holtz D, Dunton C, Green JJ, et al. Nanoparticle-Delivered Suicide Gene Therapy Effectively Reduces Ovarian Tumor Burden in Mice. Cancer Res. 2009;69:6184–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tanos V, Prus D, Ayesh S, Weinstein D, Tykocinski ML, De-Groot N, et al. Expression of the imprinted H19 oncofetal RNA in epithelial ovarian cancer1This work was presented in part in the 14th International Conference on Human Tumor Markers, June 15–19, 1997, Jerusalem, Israel.1. Eur J Obstet Gynecol Reprod Biol. 1999;85:7–11.

    Article  CAS  PubMed  Google Scholar 

  69. Mizrahi A, Czerniak A, Levy T, Amiur S, Gallula J, Matouk I, et al. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J Transl Med. 2009;7:69.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Mizrahi A, Czerniak A, Ohana P, Amiur S, Gallula J, Matouk I, et al. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report. J Med Case Rep. 2010;4:228.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Lavie O, Edelman D, Levy T, Fishman A, Hubert A, Segev Y, et al. A phase 1/2a, dose-escalation, safety, pharmacokinetic, and preliminary efficacy study of intraperitoneal administration of BC-819 (H19-DTA) in subjects with recurrent ovarian/peritoneal cancer. Arch Gynecol Obstet. 2017;295:751–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cocco E, Deng Y, Shapiro EM, Bortolomai I, Lopez S, Lin K, et al. Dual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells. Mol Cancer Ther. 2017;16:323–33.

    Article  CAS  PubMed  Google Scholar 

  73. Stirpe F, Olsnes S, Pihl A. Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavalin A. J Biol Chem. 1980;255:6947–53.

    Article  CAS  PubMed  Google Scholar 

  74. Gou M, Men K, Zhang J, Li Y, Song J, Luo S, et al. Efficient inhibition of C-26 colon carcinoma by VSVMP gene delivered by biodegradable cationic nanogel derived from polyethyleneimine. ACS Nano. 2010;4:5573–84.

    Article  CAS  PubMed  Google Scholar 

  75. Bai Y, Gou M, Yi T, Yang L, Liu L, Lin X, et al. Efficient Inhibition of Ovarian Cancer by Gelonin Toxin Gene Delivered by Biodegradable Cationic Heparin-polyethyleneimine Nanogels. Int J Med Sci. 2015;12:397–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zhao J, Wen Y, Li Q, Wang Y, Wu H, Xu J, et al. A promising cancer gene therapy agent based on the matrix protein of vesicular stomatitis virus. FASEB J. 2008;22:4272–80.

    Article  CAS  PubMed  Google Scholar 

  77. Scaranti M, Cojocaru E, Banerjee S, Banerji U. Exploiting the folate receptor α in oncology. Nat Rev Clin Oncol. 2020;17:349–59.

    Article  PubMed  Google Scholar 

  78. Mornet E, Carmoy N, Lainé C, Lemiègre L, Le Gall T, Laurent I, et al. Folate-equipped nanolipoplexes mediated efficient gene transfer into human epithelial cells. Int J Mol Sci. 2013;14:1477–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. He ZY, Deng F, Wei XW, Ma CC, Luo M, Zhang P, et al. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex. Sci Rep. 2016;6:23764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Haunschild CE, Tewari KS. The current landscape of molecular profiling in the treatment of epithelial ovarian cancer. Gynecol Oncol. 2021;160:333–45.

    Article  CAS  PubMed  Google Scholar 

  81. Kastenhuber ER, Lowe SW. Putting p53 in Context. Cell 2017;170:1062–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zeimet AG, Marth C. Why did p53 gene therapy fail in ovarian cancer? Lancet Oncol. 2003;4:415–22.

    Article  CAS  PubMed  Google Scholar 

  83. Ryu SY, Kim K, Lee WS, Kwon HC, Lee KH, Kim CM, et al. Synergistic growth inhibition by combination of adenovirus mediated p53 transfer and cisplatin in ovarian cancer cell lines. J Gynecol Oncol. 2009;20:48–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Miettinen S, Ylikomi T. Concomitant exposure of ovarian cancer cells to docetaxel, CPT-11 or SN-38 and adenovirus-mediated p53 gene therapy. Anticancer Drugs. 2009;20:589–600.

    Article  CAS  PubMed  Google Scholar 

  85. Gu J, Tang Y, Liu Y, Guo H, Wang Y, Cai L, et al. Murine double minute 2 siRNA and wild-type p53 gene therapy enhances sensitivity of the SKOV3/DDP ovarian cancer cell line to cisplatin chemotherapy in vitro and in vivo. Cancer Lett. 2014;343:200–9.

    Article  CAS  PubMed  Google Scholar 

  86. Guo X, Fang Z, Zhang M, Yang D, Wang S, Liu K. A Co-Delivery System of Curcumin and p53 for Enhancing the Sensitivity of Drug-Resistant Ovarian Cancer Cells to Cisplatin. Molecules 2020;25:E2621.

    Article  Google Scholar 

  87. Bowman KR, Kim JH, Lim CS. Narrowing the field: cancer-specific promoters for mitochondrially-targeted p53-BH3 fusion gene therapy in ovarian cancer. J Ovarian Res. 2019;12:38.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Lu P, Redd Bowman KE, Brown SM, Joklik-Mcleod M, Vander Mause ER, Nguyen HTN, et al. p53-Bad: A Novel Tumor Suppressor/Proapoptotic Factor Hybrid Directed to the Mitochondria for Ovarian Cancer Gene Therapy. Mol Pharm. 2019;16:3386–98.

    Article  CAS  PubMed  Google Scholar 

  89. Li Z, Ding Q, Li Y, Miller SA, Abbruzzese JL, Hung MC. Suppression of pancreatic tumor progression by systemic delivery of a pancreatic-cancer-specific promoter driven Bik mutant. Cancer Lett. 2006;236:58–63.

    Article  CAS  PubMed  Google Scholar 

  90. Tsuruta Y, Mandai M, Konishi I, Kuroda H, Kusakari T, Yura Y, et al. Combination effect of adenovirus-mediated pro-apoptotic bax gene transfer with cisplatin or paclitaxel treatment in ovarian cancer cell lines. Eur J Cancer. 2001;37:531–41.

    Article  CAS  PubMed  Google Scholar 

  91. Huang X, Lin T, Gu J, Zhang L, Roth JA, Stephens LC, et al. Combined TRAIL and Bax gene therapy prolonged survival in mice with ovarian cancer xenograft. Gene Ther. 2002;9:1379–86.

    Article  CAS  PubMed  Google Scholar 

  92. Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, et al. Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene 2009;28:209–18.

    Article  CAS  PubMed  Google Scholar 

  93. Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, et al. CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells. 2009;27:2875–83.

    Article  CAS  PubMed  Google Scholar 

  94. Long Q, Yang R, Lu W, Zhu W, Zhou J, Zheng C, et al. Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells. Oncol Rep. 2017;37:155–62.

    Article  PubMed  Google Scholar 

  95. Dai Y, Zhao XJ, Li F, Yuan Y, Yan DM, Cao H, et al. Truncated Bid Regulates Cisplatin Response via Activation of Mitochondrial Apoptosis Pathway in Ovarian Cancer. Human Gene Therapy. 2020. Accessed 2022 Feb 9. https://www.liebertpub.com/doi/abs/10.1089/hum.2019.206

  96. Yuan X, Gajan A, Chu Q, Xiong H, Wu K, Wu GS. Developing TRAIL/TRAIL death receptor-based cancer therapies. Cancer Metastasis Rev. 2018;37:733–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. von Karstedt S, Montinaro A, Walczak H. Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy. Nat Rev Cancer. 2017;17:352–66.

    Article  Google Scholar 

  98. Zhong H, Wang H, Li J, Huang Y. TRAIL-based gene delivery and therapeuticstrategies. Acta Pharm Sin. 2019;40:1373–85.

    Article  CAS  Google Scholar 

  99. Yin PT, Shah S, Pasquale NJ, Garbuzenko OB, Minko T, Lee KB. Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer. Biomaterials. 2016;81:46–57.

    Article  CAS  PubMed  Google Scholar 

  100. Kuroki LM, Jin X, Dmitriev IP, Kashentseva EA, Powell MA, Mutch DG, et al. Adenovirus platform enhances transduction efficiency of human mesenchymal stem cells: An opportunity for cellular carriers of targeted TRAIL-based TR3 biologics in ovarian cancer. PLOS ONE. 2017;12:e0190125.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Domcke S, Sinha R, Levine DA, Sander C, Schultz N. Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun. 2013;4:2126.

    Article  PubMed  Google Scholar 

  102. Elias KM, Emori MM, Papp E, MacDuffie E, Konecny GE, Velculescu VE, et al. Beyond genomics: critical evaluation of cell line utility for ovarian cancer research. Gynecol Oncol. 2015;139:97–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Beaufort CM, Helmijr JCA, Piskorz AM, Hoogstraat M, Ruigrok-Ritstier K, Besselink N, et al. Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes. PLoS One. 2014;9:e103988.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Anglesio MS, Wiegand KC, Melnyk N, Chow C, Salamanca C, Prentice LM, et al. Type-specific cell line models for type-specific ovarian cancer research. PLoS One. 2013;8:e72162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Gao Y, Men K, Pan C, Li J, Wu J, Chen X, et al. Functionalized DMP-039 Hybrid Nanoparticle as a Novel mRNA Vector for Efficient Cancer Suicide Gene Therapy. Int J Nanomed. 2021;16:5211–32.

    Article  Google Scholar 

  106. Erkan EP, Senfter D, Madlener S, Jungwirth G, Ströbel T, Saydam N, et al. Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo. Cancer Gene Ther. 2017;24:38–44.

    Article  CAS  PubMed  Google Scholar 

  107. Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, et al. Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth. Mol Ther. 2013;21:101–8.

    Article  CAS  PubMed  Google Scholar 

  108. Rojas V, Hirshfield K, Ganesan S, Rodriguez-Rodriguez L. Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment. IJMS. 2016;17:2113.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Whartenby KA, Darnowski JW, Freeman SM, Yurasha K, Calabresi P. Recombinant interferon alpha2a synergistically enhances ganciclovir-mediated tumor cell killing in the herpes simplex virus thymidine kinase system. Cancer Gene Ther. 1999;6:402–8.

    Article  CAS  PubMed  Google Scholar 

  110. Ziller C, Lincet H, Muller CD, Staedel C, Behr JP, Poulain L. The cyclin-dependent kinase inhibitor p21(cip1/waf1) enhances the cytotoxicity of ganciclovir in HSV-tk transfected ovarian carcinoma cells. Cancer Lett. 2004;212:43–52.

    Article  CAS  PubMed  Google Scholar 

  111. Sato T, Serikawa T, Sekine M, Aoki Y, Tanaka K. Increased efficiency of cisplatin-resistant cell lines to DNA-mediated gene transfer with cationic liposome. J Obstet Gynaecol Res. 2005;31:368–74.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Adeel Nasir for reading and reviewing the final manuscript.

Funding

This work was supported by “Association de Transfusion Sanguine et de Biogénétique Gaétan Saleün” (France), “Conseil Régional de Bretagne” (France), “Ligue contre le cancer” (France), “Association Française contre les Myopathies” (France) and “Vaincre la Mucoviscidose (France). Quoc Manh Nguyen is a recipient of a PhD fellowship from the “Ministère de l’Enseignement supérieur, de la Recherche et de l’Innovation” (Paris, France).

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Author notes

  1. These authors contributed equally: Tristan Montier, Frédérique d’Arbonneau.

Authors and Affiliations

  1. Univ Brest, Inserm, EFS, UMR 1078, GGB, GTCA team, “Gene Transfer and Combined therapeutic Approaches”, CHU de Brest, 22 avenue Camille Desmoulins, F-29200, Brest, France

    Quoc Manh Nguyen, Pierre-François Dupré, Tanguy Haute, Tristan Montier & Frédérique d’Arbonneau

  2. CHU de Brest, Service de Chirurgie Gynécologique, F-29200, Brest, France

    Pierre-François Dupré

  3. CHU de Brest, Service de Génétique Médicale et de Biologie de la Reproduction, Centre de Référence des Maladies Rares “Maladies Neuromusculaires”, F-29200, Brest, France

    Tristan Montier

  4. CHU de Brest, Service d’Odontologie, UFR d’Odontologie de Brest, F-29200, Brest, France

    Frédérique d’Arbonneau

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  1. Quoc Manh Nguyen
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  2. Pierre-François Dupré
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Writing-original draft preparation: QMN; review and editing: PFD, TH, TM, FD. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tristan Montier or Frédérique d’Arbonneau.

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Nguyen, Q.M., Dupré, PF., Haute, T. et al. Suicide gene strategies applied in ovarian cancer studies. Cancer Gene Ther 30, 812–821 (2023). https://doi.org/10.1038/s41417-023-00590-6

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