JAK/STAT Is a Main Signaling Pathway in Renal Carcinoma: A Systematic Review of Therapeutic Potential

Abstract

Context: Renal cell carcinoma (RCC) is a common cancer that is a urogenital cancer. Cell destruction and tumor metastasis are carried out in the context of a flow of immune changes that are carried out through signaling pathways such as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Objectives: In this systematic review, we investigated the role of JAK/STAT signaling in the treatment and pathology of RCC. Methods: This systematic review was written on the basis of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2014 - 2024 were extracted from the Web of Science, PubMed, and Scopus databases. We extracted drug inhibitors, angiogenesis factors, and necrotic factors associated with JAK/STAT signaling in RCC. Results: We reviewed 13 studies and concluded that JAK/STAT was the master signaling pathway that caused immune suppression and stimulation of angiogenesis, thus fostering RCC metastasis. Among the STAT proteins, STAT3 registered the highest frequent signaling activity in human RCC. STAT1, STAT3, and STAT6 were also implicated in phosphorylated interferon-γ (IFN-γ) and IFN-α pathways. Suppression of the JAK2-STAT1/STAT3 pathway increases suppressor of cytokine signaling 3 (SOCS 3) levels. Wogonin inhibits STAT3, vascular endothelial growth factor A (VEGFA), and epidermal growth factor receptor (EGFR), as ruxolitinib inhibits JAK/STAT and AG490, which are specific for the JAK pathway. Conclusions: The JAK/STAT shows high therapeutic potential for RCC treatment, which is related to the tumor growth stage and prognosis. This pathway could be an elective treatment for RCC patients.