STAT3 is frequently phosphorylated and activated in breast and ovarian cancers, where cytokines and growth factors up-regulate STAT3 and stimulate proliferation.
Constitutively activated signal transducer and activator of transcription 3 (STAT3) plays an important role in the formation of many tumors including ovarian cancer.
Signal transducer and activator of transcription 3 (STAT3) is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer.
The aim of this study is to investigate whether the STAT3 inhibitor HO-3867, a novel curcumin analog, has a therapeutic effect on BRCA1-mutated ovarian cancer.
Hyperactive EGFR signaling through Stat3 and the Jak-Stat3 activity together promote ovarian cancer progression to cisplatin resistance and therefore represent targets for preventing the development of cisplatin resistance and the recurrent disease during cisplatin therapy in ovarian cancer.
Altogether, these findings emphasize the importance of Stat3 in cisplatin resistance in ovarian cancer and provide a further impetus to clinically evaluate biological modifiers that may circumvent cisplatin resistance in patients with chemoresistant ovarian cancer.
Our results offer preclinical proof-of-concept for HO-3867 as a selective STAT3 inhibitor to treat ovarian cancer and other solid tumors where STAT3 is widely upregulated.
JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in patients with ovarian cancer.
Our findings suggest that a combined approach of targeting high-invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting low-invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.
Results of the present study suggested that combined therapy with eukaryotic co-expression of the plasmid‑carrying STAT3-specific siRNA and LKB1 is a novel and efficient treatment strategy for human ovarian cancer.
We further demonstrated that a STAT3/JAK2 inhibitor could potently sensitize platinum-resistant cells to carboplatin and suppress their growth in vivo Our findings offer a mechanistic rationale to target the PBX1/STAT3 axis to antagonize a key mechanism of chemoresistance in ovarian cancers and possibly other human cancers.
Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways.
Intriguingly, we demonstrated that M-MDSC could be readily induced by ascitic fluids (AF) from OC patients, which was predominantly dependent on IL-6, IL-10 and STAT3 activation as neutralization of IL-6 and/or IL-10 or inhibition of STAT3 abrogated MDSC's expansion while recombinant IL-6 and IL-10 recapitulated the expansive effect of AF; furthermore, predominantly elevated levels of IL-6 and IL-10 has been noted in the AF which was positively correlated with the abundance of M-MDSC as well as poor prognosis of OC patients.