The Sentinel Principle

Small, Subtle Changes in Your Messenger RNA (mRNA) Can Identify Cancer Early - And We've Developed the Science that Finds Them

Most people think of cancer as changes, or mutations, in the sequence of DNA that lead to uncontrolled cell division. However, in between DNA and proteins (your cell's building blocks) is another layer of information called messenger RNA (mRNA) and it is a crucial link to finding cancer. Changes in mRNA expression can be measured in blood and serve as specific early cancer indicators for cancer and other diseases. StageZero Life Sciences discovered this principle, named it the Sentinel Principle®, and patented the technology platform behind it. The Sentinel Principle has already been used to develop the first liquid biopsy for Colorectal Cancer (ColonSentry®) and is the foundation of Aristotle® - our next generation test for multiple cancers.

Our Patented Sentinel Principle Technology

The Sentinel Principle®, a platform technology developed by StageZero Life Sciences, is based on the concept that all clinical conditions and body states, including those resulting from disease or in response to treatment, generate characteristic gene expression signatures in the blood.

As blood circulates, communication occurs between cells in blood and tissue.
Subtle changes that occur in cells due to injury or disease trigger detectable changes in cell expression.
Profiling these changes generates unique molecular biomarkers that reflect disease activity.
These molecular biomarkers can be used to identify disease-specific signatures.
Gene expression signatures are discrete and specific to each disease state.

One of the strengths of the Sentinel Principle is its flexibility. Applying it to different disease areas enables our scientists to generate specific combinations of biomarkers for numerous applications and medical conditions. This enables us to provide consultation to patients and clinicians on the presence of molecular biomarkers and their reflection of disease activity, and allows us to focus on the clinical questions and diseases with the greatest unmet need and largest opportunities to improve care.

ColonSentry®

The First Liquid Biopsy for Colorectal Cancer Detection

ColonSentry® is a proprietary liquid biopsy test that uses advanced gene expression (mRNA) technology for the early identification of Colorectal Cancer (CRC). ColonSentry, was the first liquid biopsy for CRC, using our patented Sentinel Principle (1)and has been used on more than 100,000 patients nationwide(2).

Validation

9,000+ Patient Study North America (4)
100,000+ Tests Performed in U.S. (2)
Finds Right & Left Sided Cancers (4)

Clinical Utility

ColonSentry requires a simple, in-office blood draw.
If the ColonSentry score is elevated in a patient at average risk, there is an increased probability the patient may have a pre-cancerous lesion or colorectal cancer (3).
Blood tests have a greater than 95% in-office compliance rate that motivates patients to comply with CRC screening(6).
ColonSentry, in advance of Colonoscopy finds 2.1-4.7x more colorectal cancers (3).

The Science

The ColonSentry® test uses quantitative real-time polymerase chain reaction (RT-PCR) to measure the RNA transcript expression of seven biomarker genes in a whole blood sample. Expression levels of six genes—ANXA3, CLEC4D, LMNB1, PRRG4, TNFAIP6, and VNN1—are each paired with the expression level of a reference gene, IL2RB, to create a genetic signature by which patients can be stratified for CRC risk. (3)

ColonSentry® specifically measures gene expression in whole blood. Tumors are known to affect the gene expression profiles of circulating leukocytes, including both myeloid cells (monocytes, macrophages, etc.) and lymphocytes (T cells, B cells, and natural killer cells).This occurs due to a unique interaction between tumor cells and the immune system that has been referred to as “cancer immunoediting.” Immunoediting comprises three stages: elimination (in which the immune system identifies cancerous and/or precancerous cells and attempts to eradicate them), equilibrium (in which the surviving tumor cells begin mutating rapidly under selection pressure from immune-system-mediated attacks), and escape (in which tumor cells that have acquired resistance proliferate uncontrollably, leading to tumor progression). (5)

"The clinical utility of ColonSentry is significant. A routine blood test for patients who have yet to comply with any form of colorectal cancer screening can be a game-changer in identifying those at elevated risk for the disease and motivating them to have their colonoscopy. In addition, routine use of a blood test that detects both left-sided and right-sided lesions can increase the effectiveness of colorectal cancer screening by revealing the potential presence of neoplasms in advance of colonoscopy."

- Robert Burakoff, MD, Site Chief for the Division of Gastroenterology and Hepatology at New York-Presbyterian Lower Manhattan Hospital and Weill Cornell Medicine,

PUblications

References

Liew CC, Ma J, Tang HC, et al. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med. 2006 Mar;147(3):126-32.
Chao S, PilcZ T, Stamtiou D, et al. Stability of the ColonSentry Colon Cancer Risk Stratfication Test. Int. J Dis Markers. 2019 IJDM-101 DOI: 10.29011/IJDM-101-100001
Marshall KW, Mohr S, Khettabi FE, et al. A blood-based biomarker panel for stratifying current risk for colorectal cancer. Int J Cancer. 2010 Mar 1;126(5):1177-86.
Chao, S et al. Blood RNA biomarker panel detects both left- and right-sided colorectal neoplasms: a case–control study. Journal of Experimental & Clinical Cancer Research 2013, 32:44
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004;22:329-60.
Liles, E. et al. Uptake of a colorectal cancer screening blood test is higher than of a fecal test offered in clinic: A randomized trial. Cancer Treatment and Research Communications 10 (2017) 27–31.