Adamska A, Domenichini A, Falasca M et al (2017) Pancreatic ductal adenocarcinoma: current and evolving therapies. Int J Mol Sci 18(7):1338

Article  PubMed  PubMed Central  Google Scholar 

Alhayyani S, McLeod L, West AC, Balic JJ, Hodges C et al (2022) Oncogenic dependency on STAT3 serine phosphorylation in KRAS mutant lung cancer. Oncogene 41(6):809–823

Article  CAS  PubMed  Google Scholar 

Balic JJ, Garama DJ, Saad MI, Yu L, West AC et al (2019) Serine-phosphorylated STAT3 promotes tumorigenesis via modulation of RNA polymerase transcriptional activity. Cancer Res 79(20):5272–5287

Article  CAS  PubMed  Google Scholar 

Bardeesy N, DePinho RA et al (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2(12):897–909

Article  CAS  PubMed  Google Scholar 

Chen CL, Cen L, Kohout J, Hutzen B, Chan C et al (2008) Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival. Mol Cancer 7:78

Article  PubMed  PubMed Central  Google Scholar 

Chen H, Bian A, Yang L, Yin X, Wang J et al (2021) Targeting STAT3 by a small molecule suppresses pancreatic cancer progression. Oncogene 40(8):1440–1457

Article  CAS  PubMed  PubMed Central  Google Scholar 

Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C et al (2011) STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 71(14):5020–5029

Article  CAS  PubMed  PubMed Central  Google Scholar 

D’Amico S, Shi J, Martin BL, Crawford HC, Petrenko O et al (2018) STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis. Genes Dev 32(17–18):1175–1187

Article  CAS  PubMed  PubMed Central  Google Scholar 

Datta J, Dai X, Bianchi A, Silva IDC, Mehra S et al (2022) Combined MEK and STAT3 inhibition uncovers stromal plasticity by enriching for cancer-associated fibroblasts with mesenchymal stem cell-like features to overcome immunotherapy resistance in pancreatic cancer. Gastroenterology 163(6):1593–1612

Article  CAS  PubMed  Google Scholar 

Dosch AR, Dai X, Reyzer ML, Mehra S, Srinivasan S et al (2020) Combined Src/EGFR Inhibition targets STAT3 signaling and induces stromal remodeling to improve survival in pancreatic cancer. Mol Cancer Res 18(4):623–631

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fields AP, Frederick LA, Regala RP (2007) Targeting the oncogenic protein kinase Ciota signalling pathway for the treatment of cancer. Biochem Soc Trans 35(Pt 5):996–1000

Article  CAS  PubMed  Google Scholar 

Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC et al (2009) Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324(5935):1713–1716

Article  CAS  PubMed  PubMed Central  Google Scholar 

Grabner B, Schramek D, Mueller KM, Moll HP, Svinka J et al (2015) Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis. Nat Commun 6:6285

Article  CAS  PubMed  Google Scholar 

Griner EM, Kazanietz MG (2007) Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer 7(4):281–294

Article  CAS  PubMed  Google Scholar 

Gruber R, Panayiotou R, Nye E, Spencer-Dene B, Stamp G, Behrens A (2016) YAP1 and TAZ control pancreatic cancer initiation in mice by direct up-regulation of JAK-STAT3 signaling. Gastroenterology 151(3):526–539

Article  CAS  PubMed  Google Scholar 

Guanizo AC, Fernando CD, Garama DJ, Gough DJ (2018) STAT3: a multifaceted oncoprotein. Growth Factors 36(1–2):1–14

Article  CAS  PubMed  Google Scholar 

He W, Wu J, Shi J, Huo Y, Dai W et al (2018) IL22RA1/STAT3 signaling promotes stemness and tumorigenicity in pancreatic cancer. Cancer Res 78(12):3293–3305

Article  CAS  PubMed  Google Scholar 

Hu X, Li J, Fu M, Zhao X, Wang W (2021) The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther 6(1):402

Article  PubMed  PubMed Central  Google Scholar 

Huynh J, Chand A, Gough D, Ernst M (2019) Therapeutically exploiting STAT3 activity in cancer - using tissue repair as a road map. Nat Rev Cancer 19(2):82–96

Article  CAS  PubMed  Google Scholar 

Inman KS, Liu Y, Scotti ML, Leitges M, Krishna M et al (2022) Prkci regulates autophagy and pancreatic tumorigenesis in mice. Cancers (basel) 14(3):796

Article  CAS  PubMed  Google Scholar 

Janes MR, Zhang J, Li LS, Hansen R, Peters U et al (2018) Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell 172(3):578–589

Article  CAS  PubMed  Google Scholar 

Kawano T, Inokuchi J, Eto M, Murata M, Kang J-H (2022) Protein kinase C (PKC) isozymes as diagnostic and prognostic biomarkers and therapeutic targets for cancer. Cancers (basel) 14(21):5425

Article  CAS  PubMed  Google Scholar 

Khan MW, Saadalla A, Ewida AH, Al-Katranji K, Al-Saoudi G et al (2018) The STAT3 inhibitor pyrimethamine displays anti-cancer and immune stimulatory effects in murine models of breast cancer. Cancer Immunol Immunother: CII 67(1):13–23

Article  CAS  PubMed  Google Scholar 

Kuroki M, O’Flaherty JT (1999) Extracellular signal-regulated protein kinase (ERK)-dependent and ERK-independent pathways target STAT3 on serine-727 in human neutrophils stimulated by chemotactic factors and cytokines. Biochem J 341(PT 3):691–696

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M et al (2011) Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 19(4):456–469

Article  CAS  PubMed  Google Scholar 

Li X, Jiang W, Dong S, Li W, Zhu W, Zhou W (2022) A novel insight for anticancer therapy of pancreatic cancer. Biomolecules 12(10):1450

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moscat J, Diaz-Meco MT, Wooten MW et al (2009) Of the atypical PKCs, Par-4 and p62: recent understandings of the biology and pathology of a PB1-dominated complex. Cell Death Diff 16(11):1426–1437

Article  CAS  Google Scholar 

Nagathihalli NS, Castellanos JA, Shi C, Beesetty Y, Reyzer ML et al (2015) Signal transducer and activator of transcription 3, mediated remodeling of the tumor microenvironment results in enhanced tumor drug delivery in a mouse model of pancreatic cancer. Gastroenterology 149(7):1932–1943

Article  CAS  PubMed  Google Scholar 

Nagathihalli NS, Castellanos JA, Lamichhane P, Messaggio F, Shi C et al (2018) Inverse correlation of STAT3 and MEK signaling mediates resistance to RAS pathway inhibition in pancreatic cancer. Cancer Res 78(21):6235–6246

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ono Y, Fuji T, Ogita K, Kikkawa U, Igarashi K et al (1998) The structure, expression, and properties of additional members of the protein kinase C family. J Biol Chem 263(14):6927–6932

Article  Google Scholar 

Peisl S, Mellenthin C, Vignot L, Gonelle-Gispert C, Bühler L et al (2021) Therapeutic targeting of STAT3 pathways in pancreatic adenocarcinoma: a systematic review of clinical and preclinical literature PLoS One 16(6):e0252397

Philips RL, Wang Y, Cheon H, Kanno Y, Gadina M et al (2022) The JAK-STAT pathway at 30: much learned, much more to do. Cell 185(21):3857–3876

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schindler C, Levy DE, Decker T et al (2007) JAK-STAT signaling: from interferons to cytokines. J Biol Chem 282(28):20059–20063

Article  CAS  PubMed  Google Scholar 

Sahu N, Chan E, Chu F, Pham T, Koeppen H et al (2017) Cotargeting of MEK and PDGFR/STAT3 pathways to treat pancreatic ductal adenocarcinoma. Mol Cancer Ther 16(9):1729–1738

Article  CAS  PubMed  Google Scholar 

Scotti ML, Bamlet WB, Smyrk TC, Fields AP, Murray NR et al (2010) Protein kinase Ciota is required for pancreatic cancer cell transformed growth and tumorigenesis. Cancer Res 70(5):2064–2074

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sharma NK, Shankar S, Srivastava RK (2014) STAT3 as an emerging molecular target in pancreatic cancer. Gastrointest Cancer 4:115–122

CAS  Google Scholar 

Shuai K, Horvath CM, Huang LH, Qureshi SA, Cowburn D et al (1994) Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell 76(5):821–828

Article  CAS