Reprogramming tumor-associated macrophages: The role of MEK-STAT3 inhibition in lung cancer

Abstract

Tumor-associated macrophages (TAMs) crucially contribute to lung cancer's advancement and escape from the immune system. TAMs, particularly the M2 phenotype, promote an immunosuppressive microenvironment, facilitating tumor growth and metastasis. The MEK-STAT3 signalling pathway is a critical mediator in this process, driving TAM reprogramming and contributing to lung cancer's resistance to treatment. Inhibiting the MEK and STAT3 pathways disrupts key cancer-promoting mechanisms, including immune evasion, angiogenesis, and metastasis. Preclinical studies have demonstrated the effectiveness of MEK inhibitors, such as trametinib and selumetinib, in synergistic therapies for NSCLC, particularly in modulating the tumor microenvironment. We analyse the present understanding of approaches that can transform TAMs via the inhibition of MEK-STAT3 with either solo or combined treatments in lung cancer therapy.