Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors

Abstract

Introduction: Breast cancer (BC) accounts for the majority of cancers among the female population. Anomalous activation of various signaling pathways has become an issue of concern. The JAK-STAT signaling pathway is activated in numerous cancers, including BC. STAT3 is widely involved in BCs, as 40 % of BCs display phosphorylated STAT3. JAK-STAT signaling is crucial for proliferation, survival, metastasis and other cellular events associated with the tumor microenvironment. Hence, targeting this pathway has become an area of interest among researchers.

Key findings: This review article focuses on the role of STAT3 in the initiation, proliferation, progression and metastasis of BC. The roles of various phytochemicals, synthetic molecules and biologicals against JAK-STAT and STAT3 in various cancers have been discussed, with special emphasis on BC.

Significance: JAK and STAT3 are involved in various phases from initiation to metastasis, and targeting this pathway is a promising approach to inhibit the various stages of BC development and to prevent metastasis. A number of phytochemicals and synthetic and biological molecules have demonstrated potential inhibitory effects on JAK and STAT3, thereby paving the way for the development of better therapeutics against BC.

Keywords: 5-fluorouracil; Biologicals; Breast cancer; Disulfiram; Flubendazole; Gandotinib; Gemcitabine; JAK-STAT; Metastasis; Metformin; Methylseleninic acid; Phytochemicals; Pracinostat; Ruxolitinib; STAT3; Salinomycin; Synthetic molecules.