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.
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®
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ARISTOTLE can detect the following cancer signatures from a single sample of blood:
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History of the ColonSentry® TestThe First Liquid Biopsy for Colorectal Cancer Detection
Validation
Clinical Utility
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) |
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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.
- 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
- 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.