While the concept of a blood-based cancer test is simple, its application has been challenging, to the point that very few new cancer biomarkers have been FDA approved in recent years. Furthermore, those currently in use, such as CA125 and PSA for ovarian and prostate cancer respectively, are substantially limited by high false positive rates and over-diagnosis. A major hurdle to the development of novel blood based biomarkers has been the technical challenge of interrogating the plasma proteome. Another obstacle has been the choice of case/control comparisons in biomarker discovery. Levels of candidate biomarkers from cancer patients are frequently compared to healthy individuals. In these studies, it is difficult to control for genetic or environmental variables, as well as non-cancerous ����confounding���� conditions. For example, inflammation and angiogenesis are hallmarks of cancer, but also occur during infections, chronic inflammation, auto-reBAY-60-7550 active diseases and other conditions that are not specific to cancer. While some biomarker studies have used inflammatory conditions as controls, this does not obviate the need to determine the range of proteins that occur with inflammatory conditions. Indeed, the fact that many candidate cancer biomarkers lack sufficient specificity to be useful argues for a new approach. Inflammation and angiogenesis play important roles at all stages of cancer progression, including tumor initiation, growth, and metastatic dissemination. Indeed, chronic inflammatory conditions are strong risk factors for cancer. Inflammation incites and promotes carcinogenesis by causing cell and genome damage, stimulating cellular turnover via cytokines and growth factor release, and creating a tissue microenvironment that can enhance invasion, migration and angiogenesis. Finally, the immune system also controls cancer progression through immunosurveillance and immunoediting. Inflammation is a complex process enacted by the host to control tissue AZD6244 side effects damage against pathogenic, traumatic, or toxic injury and is generally categorized into an acute, rapid response, a sub-acute transition phase, and a persistent but slowly evolving chronic condition. The acute inflammatory response involves a rapid delivery of blood components, plasma, neutrophils, and leukocytes to the site of infection or injury, followed by an influx of macrophages to resolve and repair the injury. Acute phase proteins found in the plasma are defined as either positive or negative depending on whether they increase or decrease during an inflammatory disorder. If an acute inflammatory response fails to resolve the damage, a transition is made to an evolving subacute stage, then to a chronic inflammatory condition. Chronic inflammation, such as that seen in some autoreactive conditions, may be ����active����. This is characterized by tissue remodeling, macrophages, T and B cells, angiogenic and other factors.