Overview

StageZero's platform technology, The Sentinel Principle®, is a based on the principle 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. 

Pioneers in Liquid Biopsy

The Sentinel Principle served as the technology platform behind the first liquid biopsy for Colorectal Cancer, ColonSentry®. ColonSentry was validated on 9,000 patients has been used on more than 100,000 patients in North America.​ 

​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. 

Our next generation test, ARISTOTLE®, is a multi-cancer blood test that can discretely detect 9 cancer signatures with high sensitivity and specificity. (2)

​Aristotle: A single blood test for pan-cancer screening. Dempsey AA, Chao S, Stamatiou D, Pilcz T, Ying J, and Burakoff R; Journal of Clinical Oncology 2020; 38:15_suppl, e15037-e15037

ARISTOTLE®

​ARISTOTLE can detect the following cancer signatures from a single sample of blood:

• Breast Cancer
• Ovarian Cancer
• Cervical Cancer
• Endometrial Cancer​
• Liver Cancer
• Colorectal Cancer
• Stomach Cancer
• ​Prostate Cancer
• Bladder Cancer​

History of the ColonSentry® Test

The First Liquid Biopsy for Colorectal Cancer Detection

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

1. 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. 
2. Aristotle: A single blood test for pan-cancer screening. Dempsey AA, Chao S, Stamatiou D, Pilcz T, Ying J, and Burakoff R; Journal of Clinical Oncology 2020; 38:15_suppl, e15037-e15037​
3. 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
4. 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. 
5. 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
6. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004;22:329-60.
7.  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.