Table 1.
Table Summary on the Role of JAK2/STAT3 Signaling Pathway in Tumorigenesis and Treatment of Different Solid Tumors
| Tumor | Molecular Mechanism of Tumorigenesis | JAK2/STAT3 Targeted Drug/Inhibitors | Mechanism of Action | Reference |
|---|---|---|---|---|
| Pancreatic cancer | KRAS-driven tumorigenesis, mutation of p53 expression, STAT3 overactivation | Triterpenoid, gemcitabine, zerumbone, EGCG, lestaurtinib, INCB-18424 | Inhibition of oncogenic KRAS, JAK2, JAK2/STAT3 | [45–53] |
| Breast cancer | ROS-mediated STAT3/VEGF signaling activation, IL-6/JAK2/STAT3 stimulation, CCL20-induced JAK2 and STAT3 phosphorylation | AG490, BP-1-102 | JAK2 inhibition, suppression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8 expression by targeting STAT3 | [54–59,118] |
| Colorectal cancer | GP130-mediated JAK2/STAT3 activation; upstream signaling regulation of PIM1 expression; miR-34c 5p/SIRT6/JAK2/STAT3; JAK2/STAT3/CCND2 signaling | Salidroside, berberine, hispidulin, and eriocalyxin B | Inhibition of JAK2 and STAT3 phosphorylation, downregulation of COX2/PGE2-mediated – and PIM1-mediated – JAK2/STAT3 signaling | [6,32,60–66] |
| Ovarian cancer | JAK2/STAT3 mediated upregulation of Bcl-xL | Niclosamide, AG490 |
Inhibition of JAK2/STAT3, downregulation of p-STAT3 and XIAP, increased expression of cleaved-PARP, reduced Bcl-xL upregulation and STAT3 phosphorylation | [68–72] |
| Esophageal squamous cell cancer | B7-H4/STAT3/IL-6 stimulation | Tocilizumab, MPT0B098 |
Inhibition of B7-H4 expression, SOCS3 mediated JAK2/STAT3 inhibition | [24,73,74] |
| Lung cancer | miR-26a-5p-JAK2/STAT3 pathway; VEGF and bFGF mediated JAK2/STAT3 signaling | Curcumin, antrocin, INCB018424, BP-1-102 |
JAK2/STAT3 inhibition by lowering JAK2 and STAT3 expression; suppression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8 expression by targeting STAT3 | [75–78,118] |
| Gastric cancer | CCK2R-mediated JAK2/STAT3/PI3K/Akt dependent COX-2 induction, decreased SIRT6 expression | OPB-31121, isocryptotanshinone | Inhibition of the constitutive activation of STAT3 in JAK/STAT signaling | [79–83] |
| Cervical cancer | Sustained JAK2/STAT3 activity | Axitinib, AG490 and propofol | Enhances antitumor effect via VEGFR2/JAK2/STAT3 signaling and EGFR/JAK2/STAT3 | [84,85] |
| Hepatocellular carcinoma | IL-6/JAK2/STAT3 mediated carcinogenesis | WP1066, pacritinib, cryptotanishinone, AZD9150 and ruxolitinib | Inhibition of IL-6/JAK2/STAT3, STAT3 inhibition | [87–89] |
| Cholangiocarcinoma | IL-6/JAK2/STAT3; HGF/c-Met/STAT3; prolactin/JAK2/STAT3 signaling | Recombinant proteins for prolactin and IL-6 antagonist are under trial | Hormonal and cytokine receptor inhibitors | [90,92,96–101] |
| Prostate cancer | Aberrant IL-6/JAK2/STAT3 signaling | AG490, S3I-201, CNTO-328, Zerumbone, AZD1480 | IL-6 ligand blocking antibody, decreased STAT3 expression, JAK2 inhibition | [102,103] |
| Melanoma | Increased JAK2/STAT3 activation by JAK2 and STAT3 overexpression | Amentoflavone analogous, atractylenoide | Attenuate JAK2 and STAT3 phosphorylation | [2,104,105] |
| Renal cell carcinoma | JAK2/STAT3 overactivity | Ginkgetin, sunitinib | STAT3 inhibition | [106,107] |
| Bladder cancer | Msi2 mediated JAK2/STAT3; STAT3 mediated expression of Bcl-xL |
Stattic, SH-4-54, WP1066, AG490, nifuroxazide | STAT3 inhibition, JAK2 inhibition |
[108–113] |
| Glioblastoma | Highly active JAK2/STAT3 | Pacritinib, WP1066 | STAT3 inhibition | [115–117] |
Abbreviations: XIAP, X-linked inhibitor of apoptosis proteins; PARP, poly ADP-ribose polymerase; EGCG, epigallocatechin-3-gallate, ROS, reactive oxygen species; EMT, epithelial-mesenchymal transition; COX2/PGE2, cyclooxygenase 2/prostaglandin E2; PIM1, provirus integration site for Moloney murine leukemia virus; CCK2R, cholecystokinin 2 receptor; SIRT6, sirtuin 6; PI3K, phosphatidyl inositol-3-kinase; VEGFR, vascular endothelial growth factor receptor; IL, interleukin.