title: Molecular determinants of lung cancer metastasis to the central nervous system.
abstract: Lung cancer remains the leading cause of cancer-related mortality worldwide. The propensity for metastasis to the central nervous system (CNS) is a major clinical hurdle contributing to the low five-year survival rate of advanced disease. CNS metastases significantly outnumber primary brain tumors and carry a dismal prognosis in part due to the inability of therapeutic agents to cross the blood brain barrier. Standard treatment using radiation has been largely ineffective in improving mortality, suggesting the need for new agents targeting the critical metastatic drivers. The genetic and molecular events governing CNS metastasis from the lung are poorly understood at this time. This review highlights genetic events associated with CNS dissemination from the lung and molecular mechanisms associated with CNS metastasis. In vivo model systems that faithfully recapitulate escape from the lung and colonization of the CNS are described as tools for understanding the metastatic phenotype and for testing new therapeutic agents. A deeper understanding of the mechanisms of lung cancer metastasis to the CNS is needed to elucidate novel therapeutic avenues towards the improvement of the mortality associated with advanced stage lung cancer.
authors: Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA ;
authors: Timothy G
authors: TG
authors: Whitsett
authors: Center for Thoracic and Esophageal Disease, Heart and Lung Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ;
authors: Landon J
authors: LJ
authors: Inge
authors: Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA ;
authors: Harshil D
authors: HD
authors: Dhruv
authors: Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA ;
authors: Philip Y
authors: PY
authors: Cheung
authors: Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA ; ; Medical Oncology, Cancer Treatment Centers of America, Goodyear, AZ, USA ;
authors: Glen J
authors: GJ
authors: Weiss
authors: Center for Thoracic and Esophageal Disease, Heart and Lung Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ;
authors: Ross M
authors: RM
authors: Bremner
authors: Departments of Surgery and Physiology, Center for Vascular and Inflammatory Diseases and the Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Jeffrey A
authors: JA
authors: Winkles
authors: Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA ;
authors: Nhan L
authors: NL
authors: Tran
keywords: CNS metastases; Lung cancer; molecular determinants