Have a personal or library account? Click to login
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 Cover

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

Open Access
|Apr 2022

References

  1. Ko YS, Jin H, Lee JS, Park SW, Chang KC, Kang KM, et al. Radioresistant breast cancer cells exhibit increased resistance to chemotherapy and enhanced invasive properties due to cancer stem cells. Oncol Rep 2018; 40: 3752-62. doi: 10.3892/or.2018.6714
  2. Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 2011; 11: 239-53. doi: 10.1038/nrc3007
  3. 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
  4. Farhood B, Khodamoradi E, Hoseini-Ghahfarokhi M, Motevaseli E, Mirtavoos-Mahyari H, Eleojo Musa A, et al. TGF-β in radiotherapy: Mechanisms of tumor resistance and normal tissues injury. Pharmacol Res 2020; 155: 104745. doi: 10.1016/j.phrs.2020.104745
  5. 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. doi: 10.3322/caac.21262
  6. Lee SY, Jeong EK, Ju MK, Jeon HM, Kim MY, Kim CH, et al. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol Cancer 2017; 16: 10. doi: 10.1186/s12943-016-0577-4
  7. Dancea HC, Shareef MM, Ahmed MM. Role of radiation-induced TGF-beta signaling in cancer therapy. Mol Cell Pharmacol 2009; 1: 44-56. doi: 10.4255/mcpharmacol.09.06
  8. 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
  9. Park SY, Kim MJ, Park SA, Kim JS, Min KN, Kim DK, et al. Combinatorial TGF-β attenuation with paclitaxel inhibits the epithelial-to-mesenchymal transition and breast cancer stem-like cells. Oncotarget 2015; 6: 37526-43. doi: 10.18632/oncotarget.6063
  10. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010; 29: 4741-51. doi: 10.1038/onc.2010.215
  11. Diepenbruck M, Christofori G. Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol 2016; 43: 7-13. doi: 10.1016/j.ceb.2016.06.002
  12. Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol 2019; 29: 212-26. doi: 10.1016/j. tcb.2018.12.001
  13. Wang Y, Yu Y, Tsuyada A, Ren X, Wu X, Stubblefield K, et al. Transforming growth factor-β regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene 2011; 30: 1470-80. doi: 10.1038/onc.2010.531
  14. Fuxe J, Vincent T, Garcia de Herreros A. Transcriptional crosstalk between TGF-β and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle 2010; 9: 2363-74. doi: 10.4161/cc.9.12.12050
  15. Keedy VL, Bauer TM, Clarke JM, Hurwitz H, Baek I, Ha I, et al. Association of TGF-β responsive signature with anti-tumor effect of vactosertib, a potent, oral TGF-β receptor type I (TGFBRI) inhibitor in patients with advanced solid tumors. [abstract]. J Clin Oncol 2018; 36(15 Suppl): 3031. doi: 10.1200/ JCO.2018.36.15_SUPPL.3031
  16. Jung SY, Hwang S, Clarke JM, Bauer TM, Keedy VL, Lee H, et al. Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study. Invest New Drugs 2020; 38: 812-20. doi: 10.1007/s10637-019-00835-y
  17. Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, et al. Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent. J Med Chem 2014; 57: 421338. doi: 10.1021/jm500115w
  18. 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
  19. Park SA, Kim MJ, Park SY, Kim JS, Lee SJ, Woo HA, et al. EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling. Cell Mol Life Sci 2015; 72: 2023-39. doi: 10.1007/s00018-014-1798-6
  20. Yoon JH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, et al. Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med 2013; 5: 1720-39. doi: 10.1002/ emmm.201302524
  21. Park S, Yang KM, Park Y, Hong E, Hong CP, Park J, et al. Identification of epithelial-mesenchymal transition-related target genes induced by the mutation of Smad3 linker phosphorylation. J Cancer Prev 2018; 23: 1-9. doi: 10.15430/JCP.2018.23.1.1
  22. Jung SY, Yug JS, Clarke JM, Bauer TM, Keedy VL, Hwang S, et al. Population pharmacokinetics of vactosertib, a new TGF-β receptor type Ι inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol 2020; 85: 173-83. doi: 10.1007/s00280-019-03979-z
  23. Servant N, Bollet MA, Halfwerk H, Bleakley K, Kreike B, Jacob L, et al. Search for a gene expression signature of breast cancer local recurrence in young women. Clin Cancer Res 2012; 18: 1704-15. doi: 10.1158/1078-0432.CCR-11-1954
  24. Jin L, Han B, Siegel E, Cui Y, Giuliano A, Cui X. Breast cancer lung metastasis: Molecular biology and therapeutic implications. Cancer Biol Ther 2018; 19: 858-68. doi: 10.1080/15384047.2018.1456599
  25. Samarakoon R, Overstreet JM, Higgins PJ. TGF-β signaling in tissue fibrosis: redox controls, target genes and therapeutic opportunities. Cell Signal 2013; 25: 264-8. doi: 10.1016/j.cellsig.2012.10.003
  26. Breitzig M, Bhimineni C, Lockey R, Kolliputi N. 4-Hydroxy-2-nonenal: a critical target in oxidative stress? Am J Physiol Cell Physiol 2016; 311: C537-C543. doi: 10.1152/ajpcell.00101.2016
  27. Langlands FE, Horgan K, Dodwell DD, Smith L. Breast cancer subtypes: response to radiotherapy and potential radiosensitisation. Br J Radiol 2013; 86: 20120601. doi: 10.1259/bjr.20120601
  28. Tripathy J, Chowdhury AR, Prusty M, Muduli K, Priyadarshini N, Reddy KS, et al. α-Lipoic acid prevents the ionizing radiation-induced epithelial-mesenchymal transition and enhances the radiosensitivity in breast cancer cells. Eur J Pharmacol 2020; 871: 172938. doi: 10.1016/j.ejphar.2020.172938
  29. Hou J, Li L, Zhu H, Chen H, Wei N, Dai M, et al. Association between breast cancer cell migration and radiosensitivity in vitro Oncol Lett 2019; 18: 687784. doi: 10.3892/ol.2019.11027
  30. Lagadec C, Vlashi E, Della Donna L, Dekmezian C, Pajonk F. Radiation-induced reprogramming of breast cancer cells. Stem Cells 2012; 30: 833-44. doi: 10.1002/stem.1058
  31. Sundahl N, Duprez F, Ost P, De Neve W, Mareel M. Effects of radiation on the metastatic process. Mol Med 2018; 24: 16. doi: 10.1186/s10020-018-0015-8
  32. 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
  33. Kim TW, Lee KW, Ahn JB, Park YS, Ock CY, Park H, et al. Tumor microenvironment based on PD-L1 and CD8 T-cell infiltration correlated with the response of MSS mCRC patients treated vactosertib in combination with pembrolizumab. [abstract]. J Immunother Cancer 2021; 9(Suppl 2): A82. Abstr. No. 74. doi: 10.1136/jitc-2021-SITC2021.074
  34. Kaowinn S, Kim J, Lee J, Shin DH, Kang CD, Kim DK, et al. Cancer upregulated gene 2 induces epithelial-mesenchymal transition of human lung cancer cells via TGF-β signaling. Oncotarget 2017; 8: 5092-110. doi: 10.18632/oncotarget.13867
  35. Chang HY, Tseng YK, Chen YC, Shu CW, Lin MI, Liou HH, et al. High snail expression predicts a poor prognosis in breast invasive ductal carcinoma patients with HER2/EGFR-positive subtypes. Surg Oncol 2018; 27: 314-20. doi: 10.1016/j.suronc.2018.05.002
  36. Wang Y, Shi J, Chai K, Ying X, Zhou BP. The role of Snail in EMT and tumorigenesis. Curr Cancer Drug Targets 2013; 13: 963-72. doi: 10.2174/15680096113136660102
  37. Yadav P, Shankar BS. Radio resistance in breast cancer cells is mediated through TGF-β signalling, hybrid epithelial-mesenchymal phenotype and cancer stem cells. Biomed Pharmacother 2019; 111: 119-30. doi: 10.1016/j. biopha.2018.12.055
  38. Wang Y, Shi J, Chai K, Ying X, Zhou BP. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol Cancer 2017; 16: 10. doi: 10.1186/s12943-016-0577-4
  39. Sim JJ, Jeong KY. Monitoring epithelial-mesenchymal transition of pancreatic cancer cells via investigation of mitochondrial dysfunction. Methods Protoc 2020; 3: 32. doi: 10.3390/mps3020032
  40. Karicheva O, Rodriguez-Vargas JM, Wadier N, Martin-Hernandez K, Vauchelles R, Magroun N, et al. PARP3 controls TGFβ and ROS driven epithelial-to-mesenchymal transition and stemness by stimulating a TG2-Snail-E-cadherin axis. Oncotarget 2016; 7: 64109-23. doi: 10.18632/oncotarget.11627
  41. Sonowal H, Ramana KV. 4-Hydroxy-Trans-2-Nonenal in the regulation of anti-oxidative and pro-inflammatory signaling pathways. Oxid Med Cell Longev 2019; 2019: 5937326. doi: 10.1155/2019/5937326
DOI: https://doi.org/10.2478/raon-2022-0012 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
Language: English
Page range: 185 - 197
Submitted on: Sep 26, 2021
Accepted on: Jan 28, 2022
Published on: Apr 7, 2022
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 times per year

© 2022 Jiwon Choi, Jiyoung Park, Ilyoung Cho, Yhunyhong Sheen, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.