The central involvement of STAT3/5 in cancer has made these molecules attractive targets for small-molecule drug development, but currently there are no direct STAT3/5 inhibitors of clinical grade available.
In this review we discuss the importance of STAT3-dependent functions in cancer, review the status of compounds designed as direct-acting STAT3 inhibitors, and describe some of the strategies for repurposing of drugs as STAT3 inhibitors for cancer therapy.
The action mechanism remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial-to-mesenchymal transition (EMT), through inhibition of Wnt-β/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription (STAT-3 and 5), pathway which is activated and up-regulated in CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat-containing protein 48 (WDR48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state.
These findings suggest that FAM64A regulates Th17 differentiation and colitis and inflammation-associated cancer by modulating transcriptional activity of STAT3.
Overall, our results elucidated a crucial role of LDOC1 in lung cancer and revealed how LDOC1 acts as a bridge between tobacco exposure and the IL-6/JAK2/STAT3 loop in this human malignancy.
Following that, apoptotic pathways, such as p53, Akt, STAT-3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin-likely targets in cancer therapy.
CD133 receptor mediated delivery of STAT3 inhibitor for simultaneous elimination of cancer cells and cancer stem cells in oral squamous cell carcinoma.
Particularly, napabucasin-a cancer stemness inhibitor targeting STAT3-driven gene transcription-has stood out with its promising clinical efficacy and safety profile.
Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and an attractive therapeutic target for cancer and other human diseases.
Cancer stem cell biomarkers CD51 and CD133 positive populations were reduced and telomerase activities were decreased with the reduced STAT3 binding to hTERT promoters.
Signal transducer and activator of transcription 3 (STAT3) is commonly hyperactive in many cancers and is associated with cancer cell proliferation, invasion, migration, and angiogenesis.
Signal transducer and activator of transcription 3 (Stat3) is a key signaling protein driving major hallmarks of cancer and represents a promising target for the development of targeted glioblastoma therapies.