Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

Article  PubMed  Google Scholar 

Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.

Article  PubMed  Google Scholar 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

Article  CAS  PubMed  Google Scholar 

Zhu YJ, Zheng B, Wang HY, Chen L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol Sin. 2017;38:614–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi Y, Zhang Z, Qu X, Zhu X, Zhao L, Wei R, et al. Roles of STAT3 in leukemia (Review). Int J Oncol. 2018;53:7–20.

CAS  PubMed  Google Scholar 

Sriuranpong V, Park JI, Amornphimoltham P, Patel V, Nelkin BD, Gutkind JS. Epidermal growth factor receptor-independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system. Cancer Res. 2003;63:2948–56.

CAS  PubMed  Google Scholar 

Banerjee K, Resat H. Constitutive activation of STAT3 in breast cancer cells: a review. Int J Cancer. 2016;138:2570–8.

Article  CAS  PubMed  Google Scholar 

Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell. 1999;98:295–303.

Article  CAS  PubMed  Google Scholar 

Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117:1281–3.

Article  CAS  PubMed  Google Scholar 

Logotheti S, Pützer BM. STAT3 and STAT5 targeting for simultaneous management of melanoma and autoimmune diseases. Cancers. 2019;11:1448.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu Y, Fuchs J, Li C, Lin J. IL-6, a risk factor for hepatocellular carcinoma: FLLL32 inhibits IL-6-induced STAT3 phosphorylation in human hepatocellular cancer cells. Cell Cycle. 2010;9:3423–7.

Article  CAS  PubMed  Google Scholar 

He G, Karin M. NF-κB and STAT3 - key players in liver inflammation and cancer. Cell Res. 2011;21:159–68.

Article  CAS  PubMed  Google Scholar 

He G, Yu GY, Temkin V, Ogata H, Kuntzen C, Sakurai T, et al. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell. 2010;17:286–97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology. 2006;130:1117–28.

Article  CAS  PubMed  Google Scholar 

Lai SC, Su YT, Chi CC, Kuo YC, Lee KF, Wu YC, et al. DNMT3b/OCT4 expression confers sorafenib resistance and poor prognosis of hepatocellular carcinoma through IL-6/STAT3 regulation. J Exp Clin Cancer Res. 2019;38:474.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen J, Jin R, Zhao J, Liu J, Ying H, Yan H, et al. Potential molecular, cellular, and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma. Cancer Lett. 2015;367:1–11.

Article  CAS  PubMed  Google Scholar 

Pandit SK, Sandrini G, Merulla J, Nobili V, Wang X, Zangari A, et al. Mitochondrial plasticity promotes resistance to sorafenib and vulnerability to STAT3 inhibition in human hepatocellular carcinoma. Cancers. 2021;13:6029.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K, et al. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br J Cancer. 2001;84:1377–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang X, Hu R, Song Z, Zhao H, Pan Z, Feng Y, et al. Sorafenib combined with STAT3 knockdown triggers ER stress-induced HCC apoptosis and cGAS-STING-mediated anti-tumor immunity. Cancer Lett. 2022;547:215880.

Article  CAS  PubMed  Google Scholar 

Jiang Y, Chen P, Hu K, Dai G, Li J, Zheng D, et al. Inflammatory microenvironment of fibrotic liver promotes hepatocellular carcinoma growth, metastasis and sorafenib resistance through STAT3 activation. J Cell Mol Med. 2021;25:1568–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shiah JV, Grandis JR, Johnson DE. Targeting STAT3 with proteolysis targeting chimeras and next-generation antisense oligonucleotides. Mol Cancer Ther. 2021;20:219–28.

Article  CAS  PubMed  Google Scholar 

Yang X, Xu L, Yang L, Xu S. Research progress of STAT3-based dual inhibitors for cancer therapy. Bioorg Med Chem. 2023;91:117382.

Article  CAS  PubMed  Google Scholar 

Baker BF, Lot SS, Kringel J, Cheng-Flournoy S, Villiet P, Sasmor HM, et al. Oligonucleotide-europium complex conjugate designed to cleave the 5’ cap structure of the ICAM-1 transcript potentiates antisense activity in cells. Nucleic Acids Res. 1999;27:1547–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vickers TA, Wyatt JR, Burckin T, Bennett CF, Freier SM. Fully modified 2’ MOE oligonucleotides redirect polyadenylation. Nucleic Acids Res. 2001;29:1293–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ward AJ, Norrbom M, Chun S, Bennett CF, Rigo F. Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides. Nucleic Acids Res. 2014;42:5871–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liang X-H, Nichols JG, Hsu C-W, Vickers TA, Crooke ST. mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway. Nucleic Acids Res. 2019;47:6900–16.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Melton DA. Injected anti-sense RNAs specifically block messenger RNA translation in vivo. Proc Natl Acad Sci USA. 1985;82:144–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prakash TP, Kawasaki AM, Wancewicz EV, Shen L, Monia BP, Ross BS, et al. Comparing in vitro and in vivo activity of 2’-O-[2-(methylamino)-2-oxoethyl]- and 2’-O-methoxyethyl-modified antisense oligonucleotides. J Med Chem. 2008;51:2766–76.

Article  CAS  PubMed  Google Scholar 

Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol. 2017;35:238–48.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Quemener AM, Bachelot L, Forestier A, Donnou-Fournet E, Gilot D, Galibert M-D. The powerful world of antisense oligonucleotides: from bench to bedside. Wiley Interdiscip Rev RNA. 2020;11:e1594.

Article  PubMed  PubMed Central  Google Scholar 

Zhu BR, Cai JM, Tang GS, Li BL, Gao F, Cui JG, et al. [Effects of STAT3 antisense oligonucleotide on proliferation and apoptosis of non-small cell lung cancer cell line A549]. Ai Zheng. 2007;26:820–7.

CAS  PubMed  Google Scholar 

Yang L, Ma X, Xiao L, Tang M, Weng X, Sun L, et al. Uniquely modified RNA oligonucleotides targeting STAT3 suppress melanoma growth both in vitro and in vivo. Cancer Biol Ther. 2009;8:2065–72.

Article  CAS  PubMed  Google Scholar 

Oweida AJ, Darragh L, Phan A, Binder D, Bhatia S, Mueller A, et al. STAT3 Modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst. 2019;111:1339–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res. 2006;12:11–9.

Article  CAS  PubMed  Google Scholar 

Lü H, Zhang Q, Yan B. [Mitochondrial mechanisms of antisense oligodeoxynucleotide Stat3 induced apoptosis in laryngeal carcinoma cell]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2012;26:316–8.

PubMed  Google Scholar 

Li WC, Ye SL, Sun RX, Liu YK, Tang ZY, Kim Y, et al. Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res. 2006;12:7140–8.

Article