Pathway of the Month
- Bone metastases play an important role in the morbidity and mortality of patients with malignant disease. Despite therapeutic advances in the treatment of solid organ malignancy such as lung cancer, less development on metastasis interventions has been forthcoming. More recent research has focused on molecular pathway manipulation in the prevention and treatment of metastatic bone disease and associated complications such as bone pain and hypercalcemia. The osteoprotegerin/receptor activator of nuclear factor-кβ ligand/receptor activator of nuclear factor-кβ pathway, which is physiologically involved in bone turnover, has been of considerable interest, and recent promising data have been revealed.
- Metastasis is characterized by the ability of cancer cells to invade into adjacent tissue, intravasate into blood or lymphatic vessels, and extravasate into a distant tissue. Metastatic disease is primarily responsible for the low 5-year survival rate of non-small cell lung cancer (NSCLC), and therefore, an understanding of the molecular mechanisms that regulate NSCLC metastasis is clearly warranted. The serine/threonine kinase and tumor suppressor LKB1 is mutated in 30% of NSCLC tumors, and recent evidence points to a prominent role in NSCLC metastasis.
- Chemokines are proinflammatory chemoattractant cytokines that regulate cell trafficking and adhesion. The CXCR4 chemokine receptor and its ligand, stromal cell derived factor (SDF-1), constitute a chemokine/receptor axis that has attracted great interest because of an increasing understanding of its role in cancer, including lung cancer. The CXCR4/SDF-1 complex activates several pathways that mediate chemotaxis, migration and secretion of angiopoietic factors. Neutralization of SDF-1 by anti-SDF-1 or anti-CXCR4 monoclonal antibody in preclinical in vivo studies results in a significant decrease of non-small cell lung cancer metastases.