Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Recombinant oncolytic virus NDV-anti-VEGFR2 enhances radiotherapy sensitivity in NSCLC by targeting VEGF signaling and impairing DNA repair

Gene Therapy volume 32, pages 517–528 (2025)Cite this article

Subjects

Abstract

Resistance to radiotherapy is a significant challenge in the clinical management of non-small cell lung cancer (NSCLC). This study investigates a novel multimodal therapeutic strategy that combines oncolytic Newcastle disease virus (NDV) with an anti-VEGFR2 single-chain variable fragment (NDV-anti-VEGFR2) to enhance radiosensitivity in NSCLC. We engineered NDV-anti-VEGFR2 and assessed its efficacy in sensitizing Calu-1 cells to radiation. In vitro results demonstrated that NDV-anti-VEGFR2 significantly inhibited tumor cell proliferation when combined with radiotherapy. In vivo experiments revealed that NDV-anti-VEGFR2, combined with radiation, achieved a tumor growth inhibition rate of 86.48%, surpassing the effects of NDV or radiation alone. Mechanistic investigations indicated that NDV-anti-VEGFR2 mitigated hypoxia by downregulating HIF-1α and impaired DNA repair pathways, as evidenced by reduced levels of RAD51 and γ-H2AX. These findings suggest that NDV-anti-VEGFR2 not only normalizes tumor vasculature but also enhances the cytotoxic effects of radiation by compromising DNA repair mechanisms. Collectively, our results support the clinical potential of NDV-anti-VEGFR2 combined with radiotherapy as a promising strategy to overcome radiotherapy resistance in NSCLC. Future studies in immunocompetent models are warranted to elucidate the immune-mediated effects of this innovative therapeutic approach.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Generation and characterization of NDV-anti-hVEGFR2.
Fig. 2: Radiosensitization of Calu-1 cells by NDV and NDV-anti-hVEGFR2 in vitro.
Fig. 3: In vivo evaluation of tumor growth inhibition by NDV, NDV-anti-mVEGFR2, radiation, NDV+radiation, and NDV-anti-mVEGFR2+radiation in Calu-1 xenograft model.
Fig. 4: Growth rate of NDV and NDV-anti-mVEGFR2 in vitro and in vivo.
Fig. 5: Immunohistochemical staining in Calu-1 xenograft tumor tissues.
Fig. 6: NDV-anti-mVEGFR2 impairs tumor DNA damage repair and blocks VEGF signaling pathway.

Similar content being viewed by others

Data availability

The data that support the findings of the study are available from the corresponding author upon reasonable request.

References

  1. Chen P, Liu Y, Wen Y, Zhou C. Non‐small cell lung cancer in China. Cancer Commun. 2022;42:937–70.

    Article  Google Scholar 

  2. Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7:170070.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kim B, Hong Y, Lee S, Liu P, Lim J, Lee Y, et al. Therapeutic implications for overcoming radiation resistance in cancer therapy. Int J Mol Sci. 2015;16:26880–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Adrian CB, Fiona AS, Conchita V. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239–53.

    Article  Google Scholar 

  5. Dohopolski M, Gottumukkala S, Gomez D, Iyengar P. Radiation therapy in non-small-cell lung cancer. Cold Spring Harb Perspect Med. 2021;11:a037713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol. 1996;41:31–9.

    Article  CAS  PubMed  Google Scholar 

  7. Sørensen BS, Horsman MR. Tumor hypoxia: impact on radiation therapy and molecular pathways. Front Oncol. 2020;10:562.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Begg K, Tavassoli M. Inside the hypoxic tumour: reprogramming of the DDR and radioresistance. Cell Death Discov. 2020;6:77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jens O. Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck-a systematic review and meta-analysis. Radiother Oncol. 2011;100:22–32.

    Article  Google Scholar 

  10. Harada H. How can we overcome tumor hypoxia in radiation therapy? J Radiat Res. 2011;52:545–56.

    Article  CAS  PubMed  Google Scholar 

  11. Barker HE, Paget JTE, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015;15:409–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nisar H, Labonté FM, Roggan MD, Schmitz C, Chevalier F, Konda B, et al. Hypoxia modulates radiosensitivity and response to different radiation qualities in A549 non-small cell lung cancer (NSCLC) cells. Int J Mol Sci. 2024;25:1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gregg LS. Intratumoral hypoxia, radiation resistance, and HIF-1. Cancer Cell. 2004;5:405–6.

    Article  Google Scholar 

  14. Benjamin JM, Yiting C, Chuan YL, Mark WD. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell. 2004;5:429–41.

    Article  Google Scholar 

  15. Kieran MW, Kalluri R, Cho YJ. The VEGF pathway in cancer and disease: responses, resistance, and the path forward. Cold Spring Harb Perspect Med. 2012;2:a006593–a006593.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Trinh XB, Tjalma WAA, Vermeulen PB, Van den Eynden G, Van der Auwera I, Van Laere SJ, et al. The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer. Br J Cancer. 2009;100:971–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Abhinand CS, Raju R, Soumya SJ, Arya PS, Sudhakaran PR. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J Cell Commun Signal. 2016;10:347–54.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Karar J, Maity A. PI3K/AKT/mTOR pathway in angiogenesis. Front Mol Neurosci. 2011;4:51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mashima T, Wakatsuki T, Kawata N, Jang M-K, Nagamori A, Yoshida H, et al. Neutralization of the induced VEGF-A potentiates the therapeutic effect of an anti-VEGFR2 antibody on gastric cancer in vivo. Sci Rep. 2021;11:15125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Winkler F, Kozin SV, Tong RT, Chae S-S, Booth MF, Garkavtsev I, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation. Cancer Cell. 2004;6:553–63.

    CAS  PubMed  Google Scholar 

  21. Li J, Huang S, Armstrong EA, Fowler JF, Harari PM. Angiogenesis and radiation response modulation after vascular endothelial growth factor receptor-2 (VEGFR2) blockade. Int J Radiat Oncol Biol Phys. 2005;62:1477–85.

    Article  CAS  PubMed  Google Scholar 

  22. Liu L, Qiao Y, Hu C, Liu Y, Xia Y, Wang L, et al. Endostatin exerts radiosensitizing effect in non-small cell lung cancer cells by inhibiting VEGFR2 expression. Clin Transl Oncol. 2015;18:18–26.

    Article  PubMed  Google Scholar 

  23. Xiao-Dong J, Peng D, Jin W, Da-An S, Jin-Ming Y. Effect of recombinant human endostatin on radiosensitivity in patients with non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;83:1272–7.

    Google Scholar 

  24. Gohara S, Shinohara K, Yoshida R, Kariya R, Tazawa H, Hashimoto M, et al. An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma. Mol Ther Oncolytics. 2022;27:141–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Touchefeu Y, Vassaux G, Harrington KJ. Oncolytic viruses in radiation oncology. Radiother Oncol. 2011;99:262–70.

    Article  CAS  PubMed  Google Scholar 

  26. Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14:642–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. O’Cathail SM, Pokrovska TD, Maughan TS, Fisher KD, Seymour LW, Hawkins MA. Combining oncolytic adenovirus with radiation—a paradigm for the future of radiosensitization. Front Oncol. 2017;7:153.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ulasov I, Omori T, Tazawa H, Yamakawa Y, Osaki S, Hasei J, et al. Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. Plos ONE. 2021;16:e0250643.

    Article  Google Scholar 

  29. Storozynsky QT, Agopsowicz KC, Noyce RS, Bukhari AB, Han X, Snyder N, et al. Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model. Cancer Lett. 2023;562:216169.

    Article  CAS  PubMed  Google Scholar 

  30. Zamarin D, Palese P. Oncolytic Newcastle disease virus for cancer therapy: old challenges and new directions. Future Microbiol. 2012;7:347–67.

    Article  CAS  PubMed  Google Scholar 

  31. Yang H, Tian J, Zhao J, Zhao Y, Zhang G. The application of Newcastle disease virus (NDV): vaccine vectors and tumor therapy. Viruses. 2024;16:886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Vijayakumar G, Palese P, Goff PH. Oncolytic Newcastle disease virus expressing a checkpoint inhibitor as a radioenhancing agent for murine melanoma. eBioMedicine. 2019;49:96–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kanthou C, Tozer G. Targeting the vasculature of tumours: combining VEGF pathway inhibitors with radiotherapy. Br J Radio. 2018;92:20180405.

    Article  Google Scholar 

  34. Tian L, Liu T, Jiang S, Cao Y, Kang K, Su H, et al. Oncolytic Newcastle disease virus expressing the co-stimulator OX40L as immunopotentiator for colorectal cancer therapy. Gene Ther. 2021;30:64–74.

    Article  PubMed  Google Scholar 

  35. Meng F, Cao Y, Su H, Liu T, Tian L, Zhang Y, et al. Newcastle disease virus expressing an angiogenic inhibitor exerts an enhanced therapeutic efficacy in colon cancer model. Plos One. 2022;17:e0264896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kehn-Hall K, Baer A. Viral concentration determination through plaque assays: using traditional and novel overlay systems. J Vis Exp. 2014;93:e52065.

  37. Wang Z, Shi X, Zhao Y, Zhou J, Zhang S, Wang J, et al. DC101, an anti-VEGFR2 agent, promotes high-endothelial venule formation and immune infiltration versus SAR131675 and fruquintinib. Biochem Biophys Res Commun. 2023;661:10–20.

    Article  CAS  PubMed  Google Scholar 

  38. Willett CG, Kozin SV, Duda DG, di Tomaso E, Kozak KR, Boucher Y, et al. Combined vascular endothelial growth factor–targeted therapy and radiotherapy for rectal cancer: theory and clinical practice. Semin Oncol. 2006;33:S35–S40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tsunekuni K, Kawakami H, Matsuoka K, Nagase H, Mitani S, Nakagawa K. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, FTD/TPI, with ramucirumab murine version DC101 in a mouse syngeneic cancer transplantation model. J Clin Med. 2020;9:4050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Falcon BL, Chintharlapalli S, Uhlik MT, Pytowski B. Antagonist antibodies to vascular endothelial growth factor receptor 2 (VEGFR-2) as anti-angiogenic agents. Pharm Ther. 2016;164:204–25.

    Article  CAS  Google Scholar 

  41. Zhong N, Zhuang W, Huang Q, Wang Q, Jin W. Apatinib inhibits the growth of small cell lung cancer via a mechanism mediated by VEGF, PI3K/Akt and Ki-67/CD31. J Cell Mol Med. 2021;25:10039–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Huen MS-Y, Ji J, Zhang Y, Redon CE, Reinhold WC, Chen AP, et al. Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay. Plos ONE. 2017;12:e0171582.

    Article  Google Scholar 

  43. Kawashima S, Kawaguchi N, Taniguchi K, Tashiro K, Komura K, Tanaka T, et al. γ‑H2AX as a potential indicator of radiosensitivity in colorectal cancer cells. Oncol Lett. 2020;20:2331–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Klein HL. The consequences of Rad51 overexpression for normal and tumor cells. DNA Repair. 2008;7:686–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Eriko K, Abhisha SD, John Ml E, Li Y, Toru O, Kazuaki T. H2AX mRNA expression reflects DNA repair, cell proliferation, metastasis, and worse survival in breast cancer. Am J Cancer Res. 2022;12:793–804.

    Google Scholar 

  46. Liu Z-L, Chen H-H, Zheng L-L, Sun L-P, Shi L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 2023;8:198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Matuszewska K, Pereira M, Petrik D, Lawler J, Petrik J. Normalizing tumor vasculature to reduce hypoxia, enhance perfusion, and optimize therapy uptake. Cancers. 2021;13:4444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol. Rev. 2011;91:1071–121.

    Article  CAS  PubMed  Google Scholar 

  49. Kozin SV, Winkler F, Garkavtsev I, Hicklin DJ, Jain RK, Boucher Y. Human tumor xenografts recurring after radiotherapy are more sensitive to anti–vascular endothelial growth factor receptor-2 treatment than treatment-naive tumors. Cancer Res. 2007;67:5076–82.

    Article  CAS  PubMed  Google Scholar 

  50. Nilsson I, Bahram F, Li X, Gualandi L, Koch S, Jarvius M, et al. VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J. 2010;29:1377–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Adelfinger M, Bessler S, Frentzen A, Cecil A, Langbein-Laugwitz J, Gentschev I, et al. Preclinical testing oncolytic vaccinia virus strain GLV-5b451 expressing an anti-VEGF single-chain antibody for canine cancer therapy. Viruses. 2015;7:4075–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vaccaro C, Bawdon R, Wanjie S, Ober RJ, Ward ES. Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Proc Natl Acad Sci USA. 2006;103:18709–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bui BP, Nguyen PL, Lee K, Cho J. Hypoxia-inducible factor-1: a novel therapeutic target for the management of cancer, drug resistance, and cancer-related pain. Cancers. 2022;14:6054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zheng Z, Su J, Bao X, Wang H, Bian C, Zhao Q, et al. Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy. Front Immunol. 2023;14:1247268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Stegeman H, Span PN, Peeters WJM, Verheijen MMG, Grénman R, Meijer TWH, et al. Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies. Future Sci OA. 2016;2:FSO84.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Ma Y, Xiu Z, Zhou Z, Huang B, Liu J, Wu X, et al. Cytochalasin H inhibits angiogenesis via the suppression of HIF-1α protein accumulation and VEGF expression through PI3K/AKT/P70S6K and ERK1/2 signaling pathways in non-small cell lung cancer cells. J Cancer. 2019;10:1997–2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhu H, Zhang S. Hypoxia inducible factor‐1α/vascular endothelial growth factor signaling activation correlates with response to radiotherapy and its inhibition reduces hypoxia‐induced angiogenesis in lung cancer. J Cell Biochem. 2018;119:7707–18.

    Article  CAS  PubMed  Google Scholar 

  58. Zhang Y, Huang H, Coleman M, Ziemys A, Gopal P, Kazmi SM, et al. VEGFR2 activity on myeloid cells mediates immune suppression in the tumor microenvironment. JCI Insight. 2021;6:e150735.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Tada Y, Togashi Y, Kotani D, Kuwata T, Sato E, Kawazoe A, et al. Targeting VEGFR2 with Ramucirumab strongly impacts effector/ activated regulatory T cells and CD8+ T cells in the tumor microenvironment. J Immunother Cancer. 2018;6:106.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Ye X, Wheeler KC, Jena MK, Pradhan BS, Nayak N, Das S, et al. VEGF may contribute to macrophage recruitment and M2 polarization in the decidua. Plos ONE. 2018;13:e0191040.

    Article  Google Scholar 

  61. Hofman L, Lawler SE, Lamfers MLM. The multifaceted role of macrophages in oncolytic virotherapy. Viruses. 2021;13:1570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Min AKT, Mimura K, Nakajima S, Okayama H, Saito K, Sakamoto W, et al. Therapeutic potential of anti-VEGF receptor 2 therapy targeting for M2-tumor-associated macrophages in colorectal cancer. Cancer Immunol, Immunother. 2020;70:289–98.

    Article  PubMed  Google Scholar 

  63. Ginting TE, Suryatenggara J, Christian S, Mathew G. Proinflammatory response induced by Newcastle disease virus in tumor and normal cells. Oncolytic Virother. 2017;6:21–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Yang H, Lee WS, Kong SJ, Kim CG, Kim JH, Chang SK, et al. STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade. J Clin Investig. 2019;129:4350–64.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work was supported by Science and Technology Project of Jiangsu Province (Category of social development) (No.BE2022769); Jiangsu Kanion Pharmaceutical Co., Ltd., a grant from 2022 Huaguoshan Innovation and Entrepreneurship Program of Lianyungang City and 2022 Innovation and Entrepreneurship Program of Jiangsu Province (JSSCRC2022452).

Author information

Author notes

  1. These authors contributed equally: Liang Liu, Liying Song, Tianyan Liu.

Authors and Affiliations

  1. Lianyungang Clinical College of Nanjing Medical University/The First People’s Hospital of Lianyungang, Lianyungang City, Jiangsu Province, China

    Liang Liu & Xiaodong Jiang

  2. Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang City, Jiangsu Province, China

    Liying Song, Kaiyuan Hui, Chenxi Hu, Lihua Zhou & yun Qiao

  3. Jiangsu Kanion Pharmaceutical Co., Ltd., Jiangning Industrial City, Economic and Technological Development Zone, Lianyungang City, Jiangsu province, China

    Tianyan Liu, Jiarui Yang, Xuelei Pi, Yuanyuan Yan, Shishi Liu, Yating Zhang, Hongna Chen, Dan Yu, Chengkai Yin, Xu Li, Chenfeng Zhang, Deshan Li, Zhenzhong Wang & Zhihang Liu

  4. Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China

    Yukai Cao

Authors
  1. Liang Liu
    View author publications

    Search author on:PubMed Google Scholar

  2. Liying Song
    View author publications

    Search author on:PubMed Google Scholar

  3. Tianyan Liu
    View author publications

    Search author on:PubMed Google Scholar

  4. Kaiyuan Hui
    View author publications

    Search author on:PubMed Google Scholar

  5. Chenxi Hu
    View author publications

    Search author on:PubMed Google Scholar

  6. Jiarui Yang
    View author publications

    Search author on:PubMed Google Scholar

  7. Xuelei Pi
    View author publications

    Search author on:PubMed Google Scholar

  8. Yuanyuan Yan
    View author publications

    Search author on:PubMed Google Scholar

  9. Shishi Liu
    View author publications

    Search author on:PubMed Google Scholar

  10. Yating Zhang
    View author publications

    Search author on:PubMed Google Scholar

  11. Hongna Chen
    View author publications

    Search author on:PubMed Google Scholar

  12. Yukai Cao
    View author publications

    Search author on:PubMed Google Scholar

  13. Lihua Zhou
    View author publications

    Search author on:PubMed Google Scholar

  14. yun Qiao
    View author publications

    Search author on:PubMed Google Scholar

  15. Dan Yu
    View author publications

    Search author on:PubMed Google Scholar

  16. Chengkai Yin
    View author publications

    Search author on:PubMed Google Scholar

  17. Xu Li
    View author publications

    Search author on:PubMed Google Scholar

  18. Chenfeng Zhang
    View author publications

    Search author on:PubMed Google Scholar

  19. Deshan Li
    View author publications

    Search author on:PubMed Google Scholar

  20. Zhenzhong Wang
    View author publications

    Search author on:PubMed Google Scholar

  21. Zhihang Liu
    View author publications

    Search author on:PubMed Google Scholar

  22. Xiaodong Jiang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Liang Liu, Zhihang Liu, Liying Song, Tianyan Liu, Deshan Li and Xiaodong Jiang designed the study. Liang Liu, Liying Song, Zhihang Liu wrote the manuscript. Liang Liu, Liying Song, Zhihang Liu and Tianyan Liu performed the main experiments and analyzed the data. Kaiyuan Hui, Chenxi Hu, Jiarui Yang, Xuelei Pi, Yuanyuan Yan, Shishi Liu, Yating Zhang, Hongna Chen, Yukai Cao, Lihua Zhou, Yun Qiao, Dan Yu, Chengkai Yin, Xu Li performed parts of the experiments. Liang Liu, Liying Song, Zhihang Liu and Deshan Li interpreted the results. Deshan Li, Chenfeng, Zhang, Zhenzhong Wang revised the manuscript and contributed to the discussion. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zhihang Liu or Xiaodong Jiang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, L., Song, L., Liu, T. et al. Recombinant oncolytic virus NDV-anti-VEGFR2 enhances radiotherapy sensitivity in NSCLC by targeting VEGF signaling and impairing DNA repair. Gene Ther 32, 517–528 (2025). https://doi.org/10.1038/s41434-025-00540-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41434-025-00540-x

This article is cited by

Search

Advanced search

Quick links