Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. Cancer J Clin. 2023;73(3):233–54.

Article  Google Scholar 

Mirzaei H, Salehi H, Sahebkar A, Avan A, Jaafari MR, Namdar A, Rezaei A, Mirzaei HR. Deciphering biological characteristics of tumorigenic subpopulations in human colorectal cancer reveals cellular plasticity. J Res Med Sci: Official J Isfahan Univ Med Sci. 2016;112(3):21–32.

Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330.

Article  CAS  PubMed  Google Scholar 

Bahrami A, Amerizadeh F, ShahidSales S, Khazaei M, Ghayour-Mobarhan M, Sadeghnia HR, Maftouh M, Hassanian SM, Avan A. Therapeutic potential of targeting wnt/β‐catenin pathway in treatment of colorectal cancer: rational and progress. J Cell Biochem. 2017;118(8):1979–83.

Article  CAS  PubMed  Google Scholar 

Tsushima H, Ito N, Tamura S, Matsuda Y, Inada M, Yabuuchi I, Imai Y, Nagashima R, Misawa H, Takeda H. Circulating transforming growth factor β1 as a predictor of liver metastasis after resection in colorectal cancer. Clin Cancer Res. 2001;7(5):1258–62.

CAS  PubMed  Google Scholar 

Teicher BA. Malignant cells, directors of the malignant process: role of transforming growth factor-beta. Cancer Metastasis Rev. 2001;20(1–2):133–43.

Article  CAS  PubMed  Google Scholar 

Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S, Kostakis A, Nikiteas N, Papavassiliou AG. TGF-beta signalling in colon carcinogenesis. Cancer Lett. 2012;314(1):1–7.

Article  CAS  PubMed  Google Scholar 

Neuzillet C, Tijeras-Raballand A, Cohen R, Cros J, Faivre S, Raymond E, de Gramont A. Targeting the TGFβ pathway for cancer therapy. Pharmacol Ther. 2015;147:22–31.

Article  CAS  PubMed  Google Scholar 

Medicherla S, Li L, Ma JY, Kapoun AM, Gaspar NJ, Liu Y-W, Mangadu R, O’Young G, Protter AA, Schreiner GF. Antitumor Activity of TGF-β, inhibitor is dependent on the microenvironment. Anticancer Res. 2007;27(6B):4149–57.

CAS  PubMed  Google Scholar 

Son JY, Park S-Y, Kim S-J, Lee SJ, Park S-A, Kim M-J, Kim SW, Kim D-K, Nam J-S, Sheen YY. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther 2014.

Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW. Novel oral transforming growth factor-β signaling inhibitor EW‐7197 eradicates CML‐initiating cells. Cancer Sci. 2016;107(2):140–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Park S-A, Kim M-J, Park S-Y, Kim J-S, Lim W, Nam J-S, Sheen YY. TIMP-1 mediates TGF-β-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling. Sci Rep. 2015;5: 16492.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yoon JH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, Sudo K, Nakae S, Han JS, Kim OH. 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(11):1720–39.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim TW, Lee KW, Ahn JB, Lee J, Ryu J, Oh B, Ock C-Y, Hwang S, Hahm KB, Kim S-J. Efficacy and safety of vactosertib and pembrolizumab combination in patients with previously treated microsatellite stable metastatic colorectal cancer. J Clin Oncol. 2021;12(2):3573–3573.

Lee K-W, Park YS, Ahn JB, Lee JK, Ryu J, Oh B, Ock C-Y, Hwang S, Hahm KB, Kim S-J. Novel TGF-β signatures in metastatic colorectal cancer patients treated with vactosertib in combination with pembrolizumab. BMJ Specialist J. 2020;21(3):154–161.

Park S-A, Kim M-J, Park S-Y, Kim J-S, Lee S-J, Woo HA, Kim D-K, Nam J-S, Sheen YY. EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling. Cell Mol Life Sci. 2015;72(10):2023–39.

Article  CAS  PubMed  Google Scholar 

Jun EJ, Park J-H, Tsauo J, Yang S-G, Kim D-K, Kim KY, Kim MT, Yoon S-H, Lim YJ, Song H-Y. EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus. Gastrointest Endosc. 2017;86(1):219–28.

Article  PubMed  Google Scholar 

Binabaj MM, Asgharzadeh F, Avan A, Rahmani F, Soleimani A, Parizadeh MR, Ferns GA, Ryzhikov M, Khazaei M, Hassanian SM. EW-7197 prevents ulcerative colitis-associated fibrosis and inflammation. J Cell Physiol. 2019;25(3):11654–11661.

Chen E, Yang F, He H, Lei L, Liu R, Du L, Dong J, Wang M, Yang J. Decreased level of RASSF6 in sporadic colorectal cancer and its anti-tumor effects both in vitro and in vivo. Oncotarget. 2016;7(15):19813.

Article  PubMed  PubMed Central  Google Scholar 

Zhang J, Wang X, Liu T, Liu S, Jing X. Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer. Drug Deliv. 2016;23(3):784–90.

Article  CAS  Google Scholar 

Guo Y, Feng X, Jiang Y, Shi X, Xing X, Liu X, Li N, Fadeel B, Zheng C. PD1 blockade enhances cytotoxicity of in vitro expanded natural killer cells towards myeloma cells. Oncotarget. 2016;7(30):48360–74.

Article  PubMed  PubMed Central  Google Scholar 

Hassanian SM, Dinarvand P, Rezaie AR. Adenosine regulates the proinflammatory signaling function of thrombin in endothelial cells. J Cell Physiol. 2014;229(9):1292–300.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asgharzadeh F, Mostafapour A, Ebrahimi S, Amerizadeh F, Sabbaghzadeh R, Hassanian SM, Fakhraei M, Farshbaf A, Ferns GA, Giovannetti E. Inhibition of angiotensin pathway via valsartan reduces tumor growth in models of colorectal cancer. Toxicol Appl Pharmcol. 2022;440:115951.

Article  CAS  Google Scholar 

Giovannetti E, Wang Q, Avan A, Funel N, Lagerweij T, Lee JH, Caretti V, van der Velde A, Boggi U, Wang Y, et al. Role of CYB5A in pancreatic cancer prognosis and autophagy modulation. J Natl Cancer Inst. 2014;106(1):djt346.

Article  PubMed  Google Scholar 

Arjmand MH, Zahedi Avval F, Barneh F, Mousavi SH, Agharzadeh F, Hashemzehi H, Soleimani A, Avan A, Fakhraie M, Nasiri SN, Mehraban S, Ferns GA, Ryzhikov M, Jafari M, Khazaei M, Hassanian SM. Intraperitoneal administration of telmisartan prevents postsurgical adhesion band formation. J Surg Res. 2020;248:171–181.

Bai J, Mei P, Zhang C, Chen F, Li C, Pan Z, Liu H, Zheng J. BRG1 is a prognostic marker and potential therapeutic target in human breast cancer. PLoS ONE. 2013;8(3): e59772.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV, Sevillano M, Nadal C, Jung P, Zhang XH-F. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22(5):571–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kehlet SN, Sanz-Pamplona R, Brix S, Leeming D, Karsdal M, Moreno V. Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients. Sci Rep. 2016;6:30599.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ikuta D, Miyake T, Shimizu T, Sonoda H, Mukaisho K-I, Tokuda A, Ueki T, Sugihara H, Tani M. Fibrosis in metastatic lymph nodes is clinically correlated to poor prognosis in colorectal cancer. Oncotarget. 2018;9(51):29574.

Article  PubMed  PubMed Central  Google Scholar 

Hawinkels LJ, ten Dijke P. Exploring anti-TGF-β therapies in cancer and fibrosis. Growth Factors. 2011;29(4):140–52.

Article  CAS  PubMed  Google Scholar 

kumar Pandurangan A, Divya T, Kumar K, Dineshbabu V, Velavan B, Sudhandiran G. Colorectal carcinogenesis: insights into the cell death and signal transduction pathways: a review. World J Gastrointest Oncol. 2018;10(9):244.

Article  Google Scholar 

Repetto O, De Paoli P, De Re V, Canzonieri V, Cannizzaro R. Levels of soluble E-cadherin in breast, gastric, and colorectal cancers. BioMed Res Int. 2014;2014.

Conti J, Thomas G. The role of tumour stroma in colorectal cancer invasion and metastasis. Cancers (Basel). 2011;3(2):2160–8.

Article  PubMed  Google Scholar 

Xl Z, Sun T, Che N, Sun D, Zhao N, Dong Xy GuQ, Yao Z. Sun Bc: Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1. J Cell Mol Med. 2011;15(3):691–700.

Article  Google Scholar 

Belotti D, Paganoni P, Manenti L, Garofalo A, Marchini S, Taraboletti G, Giavazzi R. Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer Res. 2003;63(17):5224–9.

CAS  PubMed  Google Scholar 

Lustosa SAS, de Souza Viana L, Affonso RJ, Silva SRM, Denadai MVA, de Toledo SRC, Oliveira ID, Matos D. Expression profiling using a cDNA array and immunohistochemistry for the extracellular matrix genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in colorectal carcinoma progression and dissemination. Sci World J. 2014;2014.

Katz LH, Likhter M, Jogunoori W, Belkin M, Ohshiro K, Mishra L. TGF-β signaling in liver and gastrointestinal cancers. Cancer Lett. 2016;379(2):166–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ge R, Rajeev V, Ray P, Lattime E, Rittling S, Medicherla S, Protter A, Murphy A, Chakravarty J, Dugar S. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-β type I receptor kinase in vivo. Clin Cancer Res. 2006;12(14):4315–30.

Article  CAS  PubMed  Google Scholar 

Zhang B, Halder SK, Zhang S, Datta PK. Targeting transforming growth factor-β signaling in liver metastasis of colon cancer. Cancer Lett. 2009;277(1):114–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Afzal S, Jensen SA, Sørensen JB, Henriksen T, Weimann A, Poulsen HE. Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin. Cancer Chemother Pharmacol. 2012;69(2):301–7.

Article  CAS  PubMed  Google Scholar 

Chao T, Chan L, Ju S, Tang M, Liu C, Chen P, Tzeng C, Su Y. In vivo growth suppression of CT-26 mouse colorectal cancer cells by adenovirus-expressed small hairpin RNA specifically targeting thymosin beta-4 mRNA. Cancer Gene Ther. 2014;21(9):389.

Article  CAS  PubMed  Google Scholar 

Principe DR, DeCant B, Staudacher J, Vitello D, Mangan RJ, Wayne EA, Mascariñas E, Diaz AM, Bauer J, McKinney RD. Loss of TGFβ signaling promotes colon cancer progression and tumor-associated inflammation. Oncotarget. 2017;8(3):3