CXCR4/CXCL12 in non-small-cell lung cancer metastasis to the brain

Abstract

Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC) and the pharmacological tools that may be used to interfere with this signaling axis.

Figure 1

Intracellular CXCR4/CXCL12 signaling. Association of CXCL12 with CXCR4, a G-protein couple receptor, is known to activate multiple signaling pathways. Interaction, relation and color labels: B, binding; +P, phosphorylation; TR, transcription regulation, Z, catalysis; CS, complex subunit; green link, positive effect; red link, negative effect; grey link, unknown effect.