Targeting STAT3 in Breast Cancer Using Innovative Natural and Synthetic Scaffolds to Trigger Apoptosis, Autophagy, and Halt Tumor Progression.

INTRODUCTION:Signal Transducer and Activator of Transcription 3 (STAT3) is a key mediator in Breast Cancer (BC) progression, contributing to tumor proliferation, metastasis, survival, and resistance to chemotherapy. Phosphorylation of STAT3 at tyrosine 705 promotes its dimerization and nuclear translocation, where it activates oncogenic transcriptional programs. Due to its central role in BC pathogenesis, STAT3 has emerged as a promising molecular target for therapeutic intervention. To synthesize, characterize, and evaluate the anticancer efficacy of synthetic and natural compounds with a focus on their ability to inhibit STAT3 phosphorylation, suppress breast cancer cell proliferation, and induce apoptosis and autophagy. METHODS:A comprehensive literature review was conducted using databases such as PubMed, Scopus, Relemed, and ResearchGate. Relevant studies were identified that examined the synthesis, molecular mechanisms, and therapeutic potential of STAT3 inhibitors. Synthetic derivatives and phytochemicals were considered for their inhibitory effects on STAT3 activation and associated cellular outcomes in breast cancers. RESULTS:Several synthetic and natural compounds demonstrated significant inhibitory effects on STAT3 phosphorylation, leading to reduced breast cancer cell proliferation, migration, and survival. These agents effectively induced apoptosis and, in some cases, autophagy, highlighting their multifaceted anti-tumor mechanisms and elucidating the potential of these compounds as lead candidates for further preclinical and clinical development. CONCLUSION:Targeting STAT3 can be a significant therapeutic strategy, as both synthetic and natural compounds capable of inhibiting STAT3 signaling have been shown in preclinical studies. These findings provide valuable insights for cancer biologists, molecular researchers, and clinicians to explore STAT3 inhibitors as potential breast cancer therapeutics.