Skip to content
2000
image of Gene Therapy: Transforming the Battle Against Pancreatic Cancer

Abstract

Pancreatic cancer remains one of the most aggressive and lethal malignancies, with a dismal prognosis despite advancements in conventional treatment modalities. Gene therapy has emerged as a promising approach to combat pancreatic cancer by targeting the underlying genetic alterations and harnessing the power of the immune system. This review explores the current landscape of gene therapy strategies for pancreatic cancer, including gene replacement therapy, gene silencing, immunotherapy enhancement, and oncolytic virotherapy. Gene replacement therapy aims to restore the function of tumor suppressor genes, such as TP53, while gene silencing targets oncogenes like KRAS (Kirsten rat sarcoma viral oncogene homolog) to inhibit tumor growth. Immunotherapy enhancement, particularly through chimeric antigen receptor (CAR) T-cell therapy, has shown potential in overcoming the immunosuppressive tumor microenvironment. Oncolytic viruses, engineered to replicate in and destroy cancer cells selectively, have demonstrated efficacy in preclinical models and are being evaluated in clinical trials. Recent advances, including the successful treatment of a patient with advanced pancreatic cancer using neoantigen T-cell receptor gene therapy, highlight the potential of personalized gene therapy approaches. However, challenges such as precise gene delivery, tumor heterogeneity, and ethical considerations must be addressed to realize the potential of gene therapy for pancreatic cancer fully. Ongoing research and clinical trials are expected to facilitate the way for the development of safe and effective gene therapies, offering hope for improved outcomes in pancreatic cancer.

Loading

Article metrics loading...

/content/journals/cgt/10.2174/0115665232364196250131102330
2025-02-06
2025-07-15
Loading full text...

Full text loading...

References

  1. Karpińska M. Czauderna M. Pancreas—Its functions, disorders, and physiological impact on the mammals’ organism. Front. Physiol. 2022 13 807632 10.3389/fphys.2022.807632 35431983
    [Google Scholar]
  2. Rawla P. Sunkara T. Gaduputi V. Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World J. Oncol. 2019 10 1 10 27 10.14740/wjon1166 30834048
    [Google Scholar]
  3. Khalaf N. El-Serag H.B. Abrams H.R. Thrift A.P. Burden of pancreatic cancer: From epidemiology to practice. Clin. Gastroenterol. Hepatol. 2021 19 5 876 884 10.1016/j.cgh.2020.02.054 32147593
    [Google Scholar]
  4. Mahadiuzzaman A.S.M. Dain Md Opo F.A. Alkarim S. Stem cell-based targeted therapy in pancreatic cancer: Current approaches and future prospects. Tissue Cell 2024 89 102449 10.1016/j.tice.2024.102449 38924893
    [Google Scholar]
  5. Cao L. Dong M. Jiang K. Zhu Q. Li F. Xiao Z. Tang H. Tao R. Triblock polymer PDMAEMA-co-PNIPAM-co-PMPC to deliver siKRAS for gene therapy in pancreatic cancer. Chem. Eng. J. 2024 485 149884 10.1016/j.cej.2024.149884
    [Google Scholar]
  6. Rabab SA Zaidi SMF Amjad A Pancreatic adenocarcinoma of the tail-Unveiling a rare presentation with venous thrombosis: A case report and literature review. SAGE Open Med Case Rep 2024 12 2050313X241241197 10.1177/2050313X241241197
    [Google Scholar]
  7. Buscail L. Bournet B. Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat. Rev. Gastroenterol. Hepatol. 2020 17 3 153 168 10.1038/s41575‑019‑0245‑4 32005945
    [Google Scholar]
  8. Iliescu M.G. Stanciu L.E. Uzun A.B. Cristea A.E. Motoască I. Irsay L. Iliescu D.M. Vari T. Ciubean A.D. Caraban B.M. Ciufu N. Azis O. Ciortea V.M. Assessment of integrative therapeutic methods for improving the quality of life and functioning in cancer patients—A systematic review. J. Clin. Med. 2024 13 5 1190 10.3390/jcm13051190 38592012
    [Google Scholar]
  9. Torphy R.J. Fujiwara Y. Schulick R.D. Pancreatic cancer treatment: Better, but a long way to go. Surg. Today 2020 50 10 1117 1125 10.1007/s00595‑020‑02028‑0 32474642
    [Google Scholar]
  10. Mason D. Chen Y.Z. Krishnan H.V. Sant S. Cardiac gene therapy: Recent advances and future directions. J. Control. Release 2015 215 101 111 10.1016/j.jconrel.2015.08.001 26254712
    [Google Scholar]
  11. Zhang Y. Wu Z.Y. Gene therapy for monogenic disorders: Challenges, strategies, and perspectives. J. Genet. Genomics 2024 51 2 133 143 10.1016/j.jgg.2023.08.001 37586590
    [Google Scholar]
  12. Belete TM The current status of gene therapy for the treatment of cancer. Biologics 2021 15 67 77 10.2147/BTT.S302095
    [Google Scholar]
  13. Zhao Z. Anselmo A.C. Mitragotri S. Viral vector‐based gene therapies in the clinic. Bioeng. Transl. Med. 2022 7 1 e10258 10.1002/btm2.10258 35079633
    [Google Scholar]
  14. Dwivedi M. Sanyal S. Singh S. Dwivedi M. Sanyal S. Target and gene-based therapeutic strategies against pancreatic cancer: Current and future prospects. Curr. Gene Ther. 2024 25 10.2174/0115665232320846240910055032 39318213
    [Google Scholar]
  15. Silver E. Argiro A. Hong K. Adler E. Gene therapy vector-related myocarditis. Int. J. Cardiol. 2024 398 131617 10.1016/j.ijcard.2023.131617 38030043
    [Google Scholar]
  16. Shahryari A. Burtscher I. Nazari Z. Lickert H. Engineering gene therapy: Advances and barriers. Adv. Ther. 2021 4 9 2100040 10.1002/adtp.202100040
    [Google Scholar]
  17. Martinez S. Wu S. Geuenich M. Malik A. Weber R. Woo T. Zhang A. Jang G.H. Dervovic D. Al-Zahrani K.N. Tsai R. Fodil N. Gros P. Gallinger S. Neely G.G. Notta F. Sendoel A. Campbell K. Elling U. Schramek D. In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer. Nat. Commun. 2024 15 1 5266 10.1038/s41467‑024‑49450‑3 38902237
    [Google Scholar]
  18. Long S.A. Amparo A.M. Goodhart G. Ahmad S.A. Waters A.M. Evaluation of KRAS inhibitor-directed therapies for pancreatic cancer treatment. Front. Oncol. 2024 14 1402128 10.3389/fonc.2024.1402128 38800401
    [Google Scholar]
  19. Liu S.X. Xia Z.S. Zhong Y.Q. Gene therapy in pancreatic cancer. World J. Gastroenterol. 2014 20 37 13343 13368 10.3748/wjg.v20.i37.13343 25309069
    [Google Scholar]
  20. Sun W. Shi Q. Zhang H. Yang K. Ke Y. Wang Y. Qiao L. Advances in the techniques and methodologies of cancer gene therapy. Discov. Med. 2019 27 146 45 55 30721651
    [Google Scholar]
  21. Valente J.F.A. Queiroz J.A. Sousa F. p53 as the focus of gene therapy: Past, present and future. Curr. Drug Targets 2018 19 15 1801 1817 10.2174/1389450119666180115165447 29336259
    [Google Scholar]
  22. Yamamoto Y. Gerbi S.A. Making ends meet: Targeted integration of DNA fragments by genome editing. Chromosoma 2018 127 4 405 420 10.1007/s00412‑018‑0677‑6 30003320
    [Google Scholar]
  23. Stefanoudakis D. Frountzas M. Schizas D. Michalopoulos N.V. Drakaki A. Toutouzas K.G. Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer. Curr. Issues Mol. Biol. 2024 46 4 2827 2844 10.3390/cimb46040177 38666907
    [Google Scholar]
  24. Yao Y. Wang T. Liu Y. Zhang N. Co-delivery of sorafenib and VEGF-siRNA via pH-sensitive liposomes for the synergistic treatment of hepatocellular carcinoma. Artif. Cells Nanomed. Biotechnol. 2019 47 1 1374 1383 10.1080/21691401.2019.1596943 30977418
    [Google Scholar]
  25. Wang D. Zhang F. Gao G. CRISPR-Based therapeutic genome editing: Strategies and in vivo delivery by AAV vectors. Cell 2020 181 1 136 150 10.1016/j.cell.2020.03.023 32243786
    [Google Scholar]
  26. Singh A. Trivedi P. Jain N.K. Advances in siRNA delivery in cancer therapy. Artif. Cells Nanomed. Biotechnol. 2018 46 2 274 283 10.1080/21691401.2017.1307210 28423924
    [Google Scholar]
  27. Larsson M. Huang W.T. Liu D.M. Losic D. Local co-administration of gene-silencing RNA and drugs in cancer therapy: State-of-the art and therapeutic potential. Cancer Treat. Rev. 2017 55 128 135 10.1016/j.ctrv.2017.03.004 28363142
    [Google Scholar]
  28. Kokkinos J. Ignacio R.M.C. Sharbeen G. Boyer C. Gonzales-Aloy E. Goldstein D. McCarroll J.A. Phillips P.A. Targeting the undruggable in pancreatic cancer using nano-based gene silencing drugs. Biomaterials 2020 240 119742 10.1016/j.biomaterials.2019.119742 32088410
    [Google Scholar]
  29. Lam J.K.W. Chow M.Y.T. Zhang Y. Leung S.W.S. siRNA versus miRNA as therapeutics for gene silencing. Mol. Ther. Nucleic Acids 2015 4 9 e252 10.1038/mtna.2015.23 26372022
    [Google Scholar]
  30. Garibaldi-Ríos A.F. Figuera L.E. Zúñiga-González G.M. Gómez-Meda B.C. García-Verdín P.M. Carrillo-Dávila I.A. Gutiérrez-Hurtado I.A. Torres-Mendoza B.M. Gallegos-Arreola M.P. In silico identification of dysregulated mirnas targeting KRAS gene in pancreatic cancer. Diseases 2024 12 7 152 10.3390/diseases12070152 39057123
    [Google Scholar]
  31. Li F. Dai L. Niu J. GPX2 silencing relieves epithelial–mesenchymal transition, invasion, and metastasis in pancreatic cancer by downregulating Wnt pathway. J. Cell. Physiol. 2020 235 11 7780 7790 10.1002/jcp.29391 31774184
    [Google Scholar]
  32. Farhangnia P. Khorramdelazad H. Nickho H. Delbandi A.A. Current and future immunotherapeutic approaches in pancreatic cancer treatment. J. Hematol. Oncol. 2024 17 1 40 10.1186/s13045‑024‑01561‑6 38835055
    [Google Scholar]
  33. Laface C. Memeo R. Maselli F. Santoro A. Iaia M. Ambrogio F. Laterza M. Cazzato G. Guarini C. De Santis P. Perrone M. Fedele P. Immunotherapy and pancreatic cancer: A lost challenge? Life 2023 13 7 1482 10.3390/life13071482 37511856
    [Google Scholar]
  34. Zhang Y. Zhang Z. The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell. Mol. Immunol. 2020 17 8 807 821 10.1038/s41423‑020‑0488‑6 32612154
    [Google Scholar]
  35. Tang H.Y. Cao Y.Z. Zhou Y.W. Ma Y.S. Jiang H. Zhang H. The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer. J. Adv. Res. 2024 ••• 10.1016/j.jare.2024.01.014 38244773
    [Google Scholar]
  36. Chen T. Wang M. Chen Y. Liu Y. Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors. Cancer Cell Int. 2024 24 1 133 10.1186/s12935‑024‑03315‑3 38622705
    [Google Scholar]
  37. Kankeu Fonkoua L.A. Sirpilla O. Sakemura R. Siegler E.L. Kenderian S.S. CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities. Mol. Ther. Oncolytics 2022 25 69 77 10.1016/j.omto.2022.03.009 35434273
    [Google Scholar]
  38. Maalej K.M. Merhi M. Inchakalody V.P. Mestiri S. Alam M. Maccalli C. Cherif H. Uddin S. Steinhoff M. Marincola F.M. Dermime S. CAR-cell therapy in the era of solid tumor treatment: Current challenges and emerging therapeutic advances. Mol. Cancer 2023 22 1 20 10.1186/s12943‑023‑01723‑z 36717905
    [Google Scholar]
  39. Tang H.K.C. Wang B. Tan H.X. Sarwar M.A. Baraka B. Shafiq T. Rao A.R. CAR T-cell therapy for cancer: Latest updates and challenges, with a focus on B-Lymphoid malignancies and selected solid tumours. Cells 2023 12 12 1586 10.3390/cells12121586 37371056
    [Google Scholar]
  40. Yuan C. Wang Y. Guo Z.S. Editorial: Recent advances in gene modified immune cells and oncolytic virus for cancer immunotherapy. Front. Immunol. 2024 15 1454183 10.3389/fimmu.2024.1454183 39026671
    [Google Scholar]
  41. Volpe E. Sambucci M. Battistini L. Borsellino G. Fas–Fas ligand: Checkpoint of T cell functions in multiple sclerosis. Front. Immunol. 2016 7 382 10.3389/fimmu.2016.00382 27729910
    [Google Scholar]
  42. Benmebarek M.R. Karches C.H. Cadilha B.L. Lesch S. Endres S. Kobold S. Killing mechanisms of chimeric antigen receptor (CAR) T cells. Int. J. Mol. Sci. 2019 20 6 1283 10.3390/ijms20061283 30875739
    [Google Scholar]
  43. Davenport A.J. Jenkins M.R. Programming a serial killer: CAR T cells form non-classical immune synapses. Oncoscience 2018 5 3-4 69 70 10.18632/oncoscience.406 29854873
    [Google Scholar]
  44. Davenport A.J. Cross R.S. Watson K.A. Liao Y. Shi W. Prince H.M. Beavis P.A. Trapani J.A. Kershaw M.H. Ritchie D.S. Darcy P.K. Neeson P.J. Jenkins M.R. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity. Proc. Natl. Acad. Sci. USA 2018 115 9 E2068 E2076 10.1073/pnas.1716266115 29440406
    [Google Scholar]
  45. Yuan Y. Fan J. Liang D. Wang S. Luo X. Zhu Y. Liu N. Xiang T. Zhao X. Cell surface GRP78-directed CAR-T cells are effective at treating human pancreatic cancer in preclinical models. Transl. Oncol. 2024 39 101803 10.1016/j.tranon.2023.101803 37897831
    [Google Scholar]
  46. Ramos C.A. Heslop H.E. Brenner M.K. CAR-T cell therapy for lymphoma. Annu. Rev. Med. 2016 67 1 165 183 10.1146/annurev‑med‑051914‑021702 26332003
    [Google Scholar]
  47. Bonini C. Mondino A. Adoptive T‐cell therapy for cancer: The era of engineered T cells. Eur. J. Immunol. 2015 45 9 2457 2469 10.1002/eji.201545552 26202766
    [Google Scholar]
  48. Duong C.P.M. Yong C.S.M. Kershaw M.H. Slaney C.Y. Darcy P.K. Cancer immunotherapy utilizing gene-modified T cells: From the bench to the clinic. Mol. Immunol. 2015 67 2 2, Part A 46 57 10.1016/j.molimm.2014.12.009 25595028
    [Google Scholar]
  49. Hillerdal V. Essand M. Chimeric antigen receptor-engineered T cells for the treatment of metastatic prostate cancer. BioDrugs 2015 29 2 75 89 10.1007/s40259‑015‑0122‑9 25859858
    [Google Scholar]
  50. Zhao Z. Chen Y. Francisco N.M. Zhang Y. Wu M. The application of CAR-T cell therapy in hematological malignancies: Advantages and challenges. Acta Pharm. Sin. B 2018 8 4 539 551 10.1016/j.apsb.2018.03.001 30109179
    [Google Scholar]
  51. Alemany R. Viruses in cancer treatment. Clin. Transl. Oncol. 2013 15 3 182 188 10.1007/s12094‑012‑0951‑7 23143950
    [Google Scholar]
  52. Hemminki O. dos Santos J.M. Hemminki A. Oncolytic viruses for cancer immunotherapy. J. Hematol. Oncol. 2020 13 1 84 10.1186/s13045‑020‑00922‑1 32600470
    [Google Scholar]
  53. Bai Y. Hui P. Du X. Su X. Updates to the antitumor mechanism of oncolytic virus. Thorac. Cancer 2019 10 5 1031 1035 10.1111/1759‑7714.13043 30900824
    [Google Scholar]
  54. Hamidi-Sofiani V. Rakhshi R. Moradi N. Zeynali P. Nakhaie M. Behboudi E. Oncolytic viruses and pancreatic cancer. Cancer Treat. Res. Commun. 2022 31 100563 10.1016/j.ctarc.2022.100563 35460973
    [Google Scholar]
  55. Li Y. Hong J. Jung B.K. Oh E. Yun C.O. Oncolytic Ad co-expressing decorin and Wnt decoy receptor overcomes chemoresistance of desmoplastic tumor through degradation of ECM and inhibition of EMT. Cancer Lett. 2019 459 15 29 10.1016/j.canlet.2019.05.033 31150821
    [Google Scholar]
  56. Lin D. Shen Y. Liang T. Oncolytic virotherapy: Basic principles, recent advances and future directions. Signal Transduct. Target. Ther. 2023 8 1 156 10.1038/s41392‑023‑01407‑6 37041165
    [Google Scholar]
  57. Santos Apolonio J. Lima de Souza Gonçalves V. Cordeiro Santos M.L. Silva Luz M. Silva Souza J.V. Rocha Pinheiro S.L. de Souza W.R. Sande Loureiro M. de Melo F.F. Oncolytic virus therapy in cancer: A current review. World J. Virol. 2021 10 5 229 255 10.5501/wjv.v10.i5.229 34631474
    [Google Scholar]
  58. Li L. Liu S. Han D. Tang B. Ma J. Delivery and biosafety of oncolytic virotherapy. Front. Oncol. 2020 10 475 10.3389/fonc.2020.00475 32373515
    [Google Scholar]
  59. Huang F. Wang B.R. Wu Y.Q. Wang F.C. Zhang J. Wang Y.G. Oncolytic viruses against cancer stem cells: A promising approach for gastrointestinal cancer. World J. Gastroenterol. 2016 22 35 7999 8009 10.3748/wjg.v22.i35.7999 27672294
    [Google Scholar]
  60. De S. Ehrlich M. Arrest and attack: Microtubule-targeting agents and oncolytic viruses employ complementary mechanisms to enhance anti-tumor therapy efficacy. Genes 2024 15 9 1193 10.3390/genes15091193 39336785
    [Google Scholar]
  61. Ma R. Li Z. Chiocca E.A. Caligiuri M.A. Yu J. The emerging field of oncolytic virus-based cancer immunotherapy. Trends Cancer 2023 9 2 122 139 10.1016/j.trecan.2022.10.003 36402738
    [Google Scholar]
  62. Yan Z. Zhang Z. Chen Y. Xu J. Wang J. Wang Z. Enhancing cancer therapy: The integration of oncolytic virus therapy with diverse treatments. Cancer Cell Int. 2024 24 1 242 10.1186/s12935‑024‑03424‑z 38992667
    [Google Scholar]
  63. Jiménez D.J. Javed A. Rubio-Tomás T. Seye-Loum N. Barceló C. Clinical and preclinical targeting of oncogenic pathways in PDAC: Targeted therapeutic approaches for the deadliest cancer. Int. J. Mol. Sci. 2024 25 5 2860 10.3390/ijms25052860 38474109
    [Google Scholar]
  64. Touchefeu Y. Harrington K.J. Galmiche J.P. Vassaux G. Review article: Gene therapy, recent developments and future prospects in gastrointestinal oncology. Aliment. Pharmacol. Ther. 2010 32 8 953 968 10.1111/j.1365‑2036.2010.04424.x 20937041
    [Google Scholar]
  65. Ren C. Zhang S. Chen Y. Deng K. Kuang M. Gong Z. Zhang K. Wang P. Huang P. Zhou Z. Gong A. Exploring nicotinamide adenine dinucleotide precursors across biosynthesis pathways: Unraveling their role in the ovary. FASEB J. 2024 38 14 e23804 10.1096/fj.202400453R 39037422
    [Google Scholar]
  66. Mazzacurati L. Marzulli M. Reinhart B. Miyagawa Y. Uchida H. Goins W.F. Li A. Kaur B. Caligiuri M. Cripe T. Chiocca N. Amankulor N. Cohen J.B. Glorioso J.C. Grandi P. Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV. Mol. Ther. 2015 23 1 99 107 10.1038/mt.2014.177 25200130
    [Google Scholar]
  67. Bravo S. Núñez F. Cruzat F. Cafferata E.G. De Ferrari G.V. Montecino M. Podhajcer O.L. Enhanced CRAd activity using enhancer motifs driven by a nucleosome positioning sequence. Mol. Ther. 2013 21 7 1403 1412 10.1038/mt.2013.93 23712038
    [Google Scholar]
  68. Matsunaga W. Gotoh A. Adenovirus as a vector and oncolytic virus. Curr. Issues Mol. Biol. 2023 45 6 4826 4840 10.3390/cimb45060307 37367056
    [Google Scholar]
  69. Yano S. Tazawa H. Kishimoto H. Kagawa S. Fujiwara T. Hoffman R.M. Real-time fluorescence image-guided oncolytic virotherapy for precise cancer treatment. Int. J. Mol. Sci. 2021 22 2 879 10.3390/ijms22020879 33477279
    [Google Scholar]
  70. Islam S.M.B.U. Lee B. Jiang F. Kim E.K. Ahn S.C. Hwang T.H. Engineering and characterization of oncolytic vaccinia virus expressing truncated herpes simplex virus thymidine kinase. Cancers 2020 12 1 228 10.3390/cancers12010228 31963415
    [Google Scholar]
  71. Li Y. Duan H. Yang K. Ye J. Advancements and challenges in oncolytic virus therapy for gastrointestinal tumors. Biomed. Pharmacother. 2023 168 115627 10.1016/j.biopha.2023.115627 37812894
    [Google Scholar]
  72. Na Y. Nam J.P. Hong J. Oh E. Shin H.C. Kim H.S. Kim S.W. Yun C.O. Systemic administration of human mesenchymal stromal cells infected with polymer-coated oncolytic adenovirus induces efficient pancreatic tumor homing and infiltration. J. Control. Release 2019 305 75 88 10.1016/j.jconrel.2019.04.040 31071373
    [Google Scholar]
  73. Kowalsky S.J. Liu Z. Feist M. Berkey S.E. Ma C. Ravindranathan R. Dai E. Roy E.J. Guo Z.S. Bartlett D.L. Superagonist IL-15-armed oncolytic virus elicits potent antitumor immunity and therapy that are enhanced with PD-1 blockade. Mol. Ther. 2018 26 10 2476 2486 10.1016/j.ymthe.2018.07.013 30064894
    [Google Scholar]
  74. Smith H.G. Mansfield D. Roulstone V. Kyula-Currie J.N. McLaughlin M. Patel R.R. Bergerhoff K.F. Paget J.T. Dillon M.T. Khan A. Melcher A. Thway K. Harrington K.J. Hayes A.J. PD-1 blockade following isolated limb perfusion with vaccinia virus prevents local and distant relapse of soft-tissue sarcoma. Clin. Cancer Res. 2019 25 11 3443 3454 10.1158/1078‑0432.CCR‑18‑3767 30885937
    [Google Scholar]
  75. A clinical study on oncolytic virus injection (R130) for the treatment of advanced solid tumors. Patent NCT05860374, 2023 https://clinicaltrials.gov/study/NCT05860374
  76. LOAd703 oncolytic virus therapy for pancreatic can. Patent NCT02705196, 2016 https://clinicaltrials.gov/study/NCT02705196
  77. Phase I dose escalation study of intravenous VCN-01 with or without Gemcitabine and Abraxane® in patients with advanced solid tumors. Patent NCT02045602, 2014 https://clinicaltrials.gov/study/NCT02045602
  78. A clinical study on oncolytic virus injection (R130) for the treatment of relapsed/​refractory advanced solid tumors. Patent NCT05886075, 2023 https://clinicaltrials.gov/study/NCT05886075
  79. Leidner R. Sanjuan Silva N. Huang H. Sprott D. Zheng C. Shih Y.P. Leung A. Payne R. Sutcliffe K. Cramer J. Rosenberg S.A. Fox B.A. Urba W.J. Tran E. Neoantigen T-cell receptor gene therapy in pancreatic cancer. N. Engl. J. Med. 2022 386 22 2112 2119 10.1056/NEJMoa2119662 35648703
    [Google Scholar]
  80. Galanopoulos M. Doukatas A. Gkeros F. Viazis N. Liatsos C. Room for improvement in the treatment of pancreatic cancer: Novel opportunities from gene targeted therapy. World J. Gastroenterol. 2021 27 24 3568 3580 10.3748/wjg.v27.i24.3568 34239270
    [Google Scholar]
  81. Kim S. Jung B-K. Kim J. Jeon J.H. Jang S.H. Kim M. Recombinant Newcastle disease virus harboring PTEN suppresses pancreatic ductal adenocarcinoma growth by inhibiting PI3K/AKT/mTOR signaling and promoting apoptosis. Mol. Ther. Oncol. 2024 32 4 200898
    [Google Scholar]
  82. Arabi F. Mansouri V. Ahmadbeigi N. Gene therapy clinical trials, where do we go? An overview. Biomed. Pharmacother. 2022 153 113324 10.1016/j.biopha.2022.113324 35779421
    [Google Scholar]
  83. Momose H. Kudo S. Yoshida T. Hasui N. Matsuki R. Kogure M. Sakamoto Y. Trends in the treatment of advanced pancreatic cancer. Biosci. Trends 2024 18 3 224 232 10.5582/bst.2024.01156 38987162
    [Google Scholar]
  84. Effect of intratumoral injection of gene therapy for locally advanced pancreatic cancer (THERGAP-02). Patent NCT02806687, 2016 https://clinicaltrials.gov/study/NCT02806687
  85. The Cancer of the Pancreas Screening-5 CAPS5)Study (CAPS5). Patent NCT02000089, 2013 https://clinicaltrials.gov/study/NCT02000089
  86. Adjuvant GVAX vaccine therapy in patients with pancreatic cancer. Patent NCT00389610, 2006 https://clinicaltrials.gov/study/NCT00389610
  87. Gene Therapy of Pancreatic Ductal Adenocarcinoma (TherGAP). Patent NCT01274455, 2010 https://clinicaltrials.gov/study/NCT01274455
  88. Phase I/​II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors. Patent NCT05194735, 2021 https://clinicaltrials.gov/study/NCT05194735
  89. Bhatnagar A.R. Siddiqui F. Khan G. Pompa R. Kwon D. Nyati S. Long-term follow-up of phase I trial of oncolytic adenovirus-mediated cytotoxic and Interleukin-12 gene therapy for treatment of metastatic pancreatic cancer. Biomedicines 2024 12 5 1065 10.3390/biomedicines12051065 38791027
    [Google Scholar]
  90. Luo J. KRAS mutation in pancreatic cancer. Semin. Oncol. 2021 48 1 10 18 10.1053/j.seminoncol.2021.02.003 33676749
    [Google Scholar]
  91. Hu Z.I. O’Reilly E.M. Therapeutic developments in pancreatic cancer. Nat. Rev. Gastroenterol. Hepatol. 2024 21 1 7 24 10.1038/s41575‑023‑00840‑w 37798442
    [Google Scholar]
  92. Wang J.H. Gessler D.J. Zhan W. Gallagher T.L. Gao G. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Signal Transduct. Target. Ther. 2024 9 1 78 10.1038/s41392‑024‑01780‑w 38565561
    [Google Scholar]
  93. Szczepanski J.M. Rudolf M.A. Shi J. Clinical evaluation of the pancreatic cancer microenvironment: Opportunities and challenges. Cancers 2024 16 4 794 10.3390/cancers16040794 38398185
    [Google Scholar]
  94. Dupont P. Pharmacogenomics in cancer treatment: Tailoring drug therapy based on genetic variations. Revista de Inteligencia Artificial en Medicina. 2024 15 1 203 210
    [Google Scholar]
  95. Rehan Haider Asghar Mehdi Anjum Zehra Zameer Ahmed Zameer A. Geetha Kumari Das The challenges and future of advanced therapies. Int. J. Sci. Multidiscip. Res. 2024 2 4 311 326 10.55927/ijsmr.v2i4.8628
    [Google Scholar]
  96. Selot R. Ghosh A. Recent developments in gene therapy research in India. J. Biosci. 2024 49 1 37 10.1007/s12038‑024‑00423‑0 38384245
    [Google Scholar]
  97. Munung N.S. Nnodu O.E. Moru P.O. Kalu A.A. Impouma B. Treadwell M.J. Wonkam A. Looking ahead: Ethical and social challenges of somatic gene therapy for sickle cell disease in Africa. Gene Ther. 2024 31 5-6 202 208 10.1038/s41434‑023‑00429‑7 38012299
    [Google Scholar]
/content/journals/cgt/10.2174/0115665232364196250131102330
Loading
/content/journals/cgt/10.2174/0115665232364196250131102330
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: gene therapy ; Gene ; gene silencing ; pancreatic cancer ; CAR-T-cell ; oncolytic virotherapy
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test