Pathway of the Month
- 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.
- Class IA phosphatidylinositol-3 kinases (PI3Ks) together with AKT and mammalian target of rapamycin (mTOR) comprise the central axis of a complex, interconnected signaling network that integrates signals from growth factors, insulin, nutrients and oxygen to play a critical role in controlling cell growth, proliferation, metabolism, survival, and tumor angiogenesis. De-regulation of these processes is a required hallmark of cancer1 and aberrant activation of the class IA PI3K signaling occurs frequently in many malignancies including non-small cell lung cancer (NSCLC).
- Inflammation is an important contributor to lung tumor development and progression. In addition, inflammatory signaling may promote epithelial to mesenchymal transition, development of aggressive metastatic tumor phenotypes, and play a role in resistance to targeted therapies. New insights in inflammatory signaling have led to the evaluation of combination therapies that target these specific pathways. In addition to developing the optimal combination of targeted agents, biomarker-based selection of patients who will likely benefit will be critical to the success of this strategy.