Lung cancer is the most lethal cancer worldwide and remains a challenging disease. It is responsible for the high cancer mortality rates in the US and worldwide. Over half of lung cancer patients die within one year of being diagnosed due to late-stage detection and the scarceness of late-stage treatment options. About 80% of patients with non-small cell lung cancer (NSCLC), a class of lung cancer that constitutes 80–85% of the cases, develop stage IV disease.2 Not surprisingly, the 5-year survival rate for lung cancer patients is only 16.6%.3
Accumulating evidence over the last two decades suggests a critical role for STAT3 as a point of convergence for various signaling pathways that are dysregulated in the disease.4 Persistent phosphorylation of STAT3 has been demonstrated in 22%-65% of non-small cell lung cancers (NSCLC).5 This STAT3 activation is mediated by receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and MET; cytokine receptors, such as IL-6; and non-receptor kinases, such as Src. Over expression of total, or phosphorylated, STAT3 in resected NSCLC leads to poor prognosis.