The Sentinel Principle
In the 1990’s, our company’s co-founder and Chief Scientific Officer, Dr. C.C. Liew, first proposed the Sentinel Principle, a novel approach to identifying biomarkers of body state using blood. This unique blood biomarker approach has been modified and refined with time, but is based on the scientific observation that circulating blood reflects, in a detectable way, what is occurring throughout the body. According to the principle:
- As blood circulates communication occurs between cells in blood and tissue
- Subtle changes that occur in cells due to injury or disease trigger detectable, specific changes in blood cell gene expression
- Profiling these changes generates unique molecular signatures reflecting disease activity
- These molecular signatures can be used to identify disease-specific blood biomarkers
These biomarkers are the foundation for GeneNews' highly sensitive and specific molecular diagnostic assays which are currently under development. One of the strengths of the Sentinel Principle is its flexibility. Applying it to different disease areas enables GeneNews' Scientists to generate specific combinations of biomarkers for numerous applications, indeed theoretically virtually any medical condition. This enables GeneNews to focus on the clinical questions and diseases with the greatest unmet need and largest commercial opportunities.
Among the utilities of the Sentinel Principle are:
- early diagnosis
- determining stage of disease
- identifying responders/non-responders to a specific therapy
- monitoring progression/recurrence of disease
- monitoring the effects of treatment
- monitoring treatment compliance
GeneNews has demonstrated the power of the method in over a dozen diseases and is developing molecular diagnostic tests to address specific clinical needs with a near term focus on cancer.
FIGURE LEGEND: Many factors influence gene expression in the blood. Heritable components derived from one’s parents are one source of blood based gene expression. External factors like air pollution or second hand cigarette smoke also generate gene expression changes in the body which can be manifested in blood. Internal factors such as a colon tumor for example also precipitate changes in gene expression in blood cells as they come in contact with the tumor and the body attempts to respond. Blood is obtained by standard methods and RNA extracted from the blood in order to obtain a snapshot of specific gene expression changes that are direct and specific reflections of a disease state in the body. That “snapshot” is shown on the right as a molecular signature derived from microarray anaylsis (the disease snapshot and normal snapshot are clearly different). Genes in the microarray are identified and subjected to GeneNews’ Discovery Funnel process to obtain a small, manageable number of genes that maintain the stratification between the disease signature and normal signature. These small gene panels are the basis of GeneNews’ Sentry line of products.
The broad applicability of the Sentinel Principle across a wide range of diseases and its ability to address a diverse spectrum of specific clinical questions means that it is truly a breakthrough technology.
Some diseases such as colon cancer can be diagnosed only with invasive tests like colonoscopy or with stool-based tests. Furthermore, some diseases, like ovarian cancer, are difficult to diagnose and often manifest themselves only once the disease is too advanced to treat successfully. By contrast blood samples can be obtained readily and with little discomfort to patients. Thus the Sentinel Principle is truly revolutionary for the detection of occult disease. Simple blood testing can now be used to detect previously difficult or cumbersome to diagnose conditions, often at an early stage when diseases like cancer are most curable. Since 2003 GeneNews™ scientists have been using the Sentinel Principle™ to mine the blood for bio-information that may be used to develop a full line of Sentry diagnostic tests. ColonSentry, the company’s lead Sentry product for colorectal cancer screening is powered by this award-winning technology.
Blood is a tissue comprised of cells suspended in liquid called plasma. Red and white blood cells, and platelets are the cellular components of blood and carry out blood’s many functions throughout the body. As blood circulates throughout the body it interacts with other body cells -- transporting nutrients, oxygen and biomolecules to cells and removing cellular wastes. Blood cells also deliver immune factors to sites of infection and injury. Blood is an extraordinarily dynamic and active tissue. Given all of these factors, it is not surprising that blood cells might act as first line responders to disease and thus act as "sentinels" for detection of the presence of disease in the body.