IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets

Despite significant advancements in the oncology field, lung cancer remains the leading cause of cancer-related mortality worldwide. A key contributor to the increased mortality rate is the resistance exhibited by cancer cells to standard anticancer treatments, particularly in advanced stages of the disease. Evidence indicates that chronic inflammation within the tumour microenvironment (TME) promotes tumorigenesis and contributes to resistance to immunotherapy, radiotherapy and chemotherapy. Notably, the overexpression of the cytokine interleukin-6 (IL-6) has been documented in various tumours, including lung cancer. Both tumour-associated fibroblasts (TAFs) and tumour cells constitute the predominant sources of secreted IL-6 within the TME. Various research has elucidated the role of IL-6 and its signalling pathways in facilitating therapeutic resistance, metastasis and tumour progression in lung cancer. Consequently, targeting IL-6 and/or its receptor, in conjunction with other effective anticancer treatments, represents an ideal therapeutic technique for lung cancer management. This review aims to synthesize recent evidence on the function of the IL-6/IL-6R signalling pathway in lung cancer, with a focus on its role in therapy resistance, prognosis and tumour progression, on the basis of clinical and preclinical studies.