Targeting the IL-6/STAT3 signaling pathway to reverse chemoresistance in ovarian cancer

Ovarian cancer remains one of the most lethal gynecologic malignancies worldwide, mainly because it is often diagnosed at an advanced stage and frequently develops resistance to chemotherapy. Recent studies have identified the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway as a key driver of ovarian cancer progression and treatment resistance. This review discusses the biological functions of IL-6 and STAT3 and highlights their roles in ovarian cancer development, progression, and chemoresistance. Activation of the IL-6/STAT3 pathway promotes tumor cell proliferation, survival, angiogenesis, epithelial–mesenchymal transition, invasion, and metastasis. In addition, persistent STAT3 activation contributes to an immunosuppressive tumor microenvironment by reducing anti-tumor immune responses and enhancing immune evasion. The pathway also plays an important role in chemotherapy resistance through the regulation of apoptosis, cancer stemness, metabolic adaptation, and interactions with other oncogenic signaling networks. Given its broad involvement in tumor biology, the IL-6/STAT3 axis has emerged as a promising therapeutic target. Several agents targeting IL-6, IL-6 receptors, JAK kinases, and STAT3 have shown encouraging results in preclinical and early clinical studies, particularly when combined with standard chemotherapy. A better understanding of this signaling pathway may support the development of more effective treatment strategies and improve outcomes for patients with ovarian cancer.