Vactosertib enhances radiotherapy efficacy by modulating radiation-induced tumor microenvironment remodeling in breast cancer
By: Jiyoung Park, Jiwon Choi and Yhun Yhong Sheen
References
- Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74: 229-63. doi: 10.3322/caac.21834
- Foroudi F, Tyldesley S, Walker H, Mackillop WJ. An evidence-based estimate of appropriate radiotherapy utilization rate for breast cancer. Int J Radiat Oncol Biol Phys 2002; 53: 1240-53. doi: 10.1016/s0360-3016(02)02821-3
- Delaney G, Barton M, Jacob S. Estimation of an optimal radiotherapy utilization rate for breast carcinoma: a review of the evidence. Cancer 2003; 98: 1977-86. doi: 10.1002/cncr.11740
- Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer 2015; 15: 409-25. doi: 10.1038/nrc3958
- Schaue D, McBride WH. Links between innate immunity and normal tissue radiobiology. Radiat Res 2010; 173: 406-17. doi: 10.1667/rr1931.1
- Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer 2006; 6: 702-13. doi: 10.1038/nrc1950
- Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE, Pharoah PD, et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer 2009; 9: 134-42. doi: 10.1038/nrc2587
- Massagué J. TGFβ signalling in context. Nat Rev Mol Cell Biol 2012; 13: 616-30. doi: 10.1038/nrm3434
- Pickup M, Novitskiy S, Moses HL. The roles of TGFβ in the tumour microenvironment. Nat Rev Cancer 2013; 13: 788-99. doi: 10.1038/nrc3603
- Barcellos-Hoff MH, Park C, Wright EG. Radiation and the microenvironment - tumorigenesis and therapy. Nat Rev Cancer 2005; 5: 867-75. doi: 10.1038/nrc1735
- Te?cher BA. TGFβ-d?rected therapeutics: 2020. Pharmacol Ther 2021; 217: 107666. doi: 10.1016/j.pharmthera.2020.107666
- Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, Driscoll JJ. Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol 2021; 14: 55. doi: 10.1186/s13045-021-01053-x
- Malek E, Rana PS, Swamydas M, Daunov M, Miyagi M, Murphy E, et al. The TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide in relapsed/refractory multiple myeloma: a phase 1b trial. Nat Commun 2024; 15: 7388. doi: 10.1038/s41467-024-51442-2
- Sheen YY, Kim MJ, Park SA, Park SY, Nam JS. Targeting the transforming growth factor-β signaling in cancer therapy. Biomol Ther (Seoul) 2013; 21: 323-31. doi: 10.4062/biomolther.2013.072
- Park J, Choi J, Cho I, Sheen YY. Radiotherapy-induced oxidative stress and fibrosis in breast cancer are suppressed by vactosertib, a novel, orally bioavailable TGF-β/ALK5 inhibitor. Sci Rep 2022; 12: 16104. doi: 10.1038/s41598-022-20050-9
- Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, et al. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther 2014; 13: 1704-16. doi: 10.1158/1535-7163.Mct-13-0903
- Choi J, Park J, Cho I, Sheen Y. Co-treatment with vactosertib, a novel, orally bioavailable activin receptor-like kinase 5 inhibitor, suppresses radiotherapy-induced epithelial-to-mesenchymal transition, cancer cell stemness, and lung metastasis of breast cancer. Radiol Oncol 2022; 56: 185-97. doi: 10.2478/raon-2022-0012
- Luz F, Marinho EDC, Nascimento CP, Marques LA, Duarte MBO, Delfino PFR, et al. The effectiveness of radiotherapy in preventing disease recurrence after breast cancer surgery. Surg Oncol 2022; 41: 101709. doi: 10.1016/j.suronc.2022.101709
- Lynch C, Pitroda SP, Weichselbaum RR. Radiotherapy, immunity, and immune checkpoint inhibitors. Lancet Oncol 2024; 25: e352-62. doi: 10.1016/s1470-2045(24)00075-5
- Grivennikov SI, Karin M. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 2011; 70 (Suppl 1): i104-8. doi: 10.1136/ard.2010.140145
- Bromberg J, Wang TC. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 2009; 15: 79-80. doi: 10.1016/j.ccr.2009.01.009
- Khusnurrokhman G, Wati FF. Tumor-promoting inflammation in lung cancer: a literature review. Ann Med Surg 2022; 79: 104022. doi: 10.1016/j.amsu.2022.104022
- Shen C, Liu C, Zhang Z, Ping Y, Shao J, Tian Y, et al. PD-1 Affects the immunosuppressive function of group 2 innate lymphoid cells in human non-small cell lung cancer. Front Immunol 2021; 12: 680055. doi: 10.3389/fimmu.2021.680055
- Basak U, Sarkar T, Mukherjee S, Chakraborty S, Dutta A, Dutta S, et al. Tumor-associated macrophages: an effective player of the tumor microenvironment. Front Immunol 2023; 14: 1295257. doi: 10.3389/fimmu.2023.1295257
- Hong E, Park S, Ooshima A, Hong CP, Park J, Heo JS, et al. Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models. Sci Rep 2020; 10: 2935. doi: 10.1038/s41598-020-59893-5
- Ge R, Huang GM. Targeting transforming growth factor beta signaling in metastatic osteosarcoma. J Bone Oncol 2023; 43: 100513. doi: 10.1016/j.jbo.2023.100513
- Binabaj MM, Asgharzadeh F, Rahmani F, Al-Asady AM, Hashemzehi M, Soleimani A, et al. Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer. Daru 2023; 31: 193-203. doi: 10.1007/s40199-023-00474-y
- Jank BJ, Schnoell J, Kladnik K, Sparr C, Haas M, Gurnhofer E, et al. Targeting TGF beta receptor 1 in head and neck squamous cell carcinoma. Oral Dis 2024; 30: 1114-27. doi: 10.1111/odi.14594
Language: English
Page range: 262 - 270
Submitted on: Apr 21, 2026
Accepted on: May 13, 2026
Published on: Jun 26, 2026
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
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© 2026 Jiyoung Park, Jiwon Choi, Yhun Yhong Sheen, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.