The role of the EphB4 receptor tyrosine kinase in lung cancer

Lung cancer is the most common cause of cancer death in the United States. Importantly, little progress has been made over the past three decades in its treatment success, highlighting the need for additional therapeutic targets. Receptor tyrosine kinases are frequently implicated in the progression of lung cancer, and some tyrosine kinase inhibitors are effective clinically. However, these inhibitors are frequently met with drug resistance and subsequent relapse, suggesting the importance of investigations into these mechanisms and alternative targets. The Eph RTK family, especially EphB4, has recently emerged as important players in cancer biology. Here, EphB4 is demonstrated to be overexpressed and mutated in lung cancer and to undergo copy number gains. Furthermore, inhibition of EphB4 reduces growth of lung cancer in vitro and in vivo, while expression of wild-type and mutant EphB4 promotes cell growth. Finally, investigation into EphB4 signaling reveals broad involvement in tyrosine kinase activity. Overall, this work represents the first systematic investigation of the role of EphB4 in lung cancer and identifies it as a novel therapeutic target.