BEYOND GENOMICS — THE POWER OF FUNCTIONAL PRECISION ONCOLOGY
The goal of precision oncology is to match an individual to the optimal therapy for their unique form of cancer, but clinical outcomes have lagged significantly behind its potential. Beyond genomic profiling — which provides directional information about what might work for an individual — there are new functional testing options that can help inform personalized cancer treatment strategies.
4 Things To Know About Functional Precision Oncology Technologies:
1.
Functional Precision Oncology Can Capture Cancer’s Complexities
Cancers are complex, dynamic and adaptive,1 and a tumor’s genetic makeup can change over time. Genetic testing provides a static snapshot of genetic mutations and other aberrations within a tumor fragment, which can provide directional information about what targeted therapies might be effective for that individual. But contrary to popular belief, genetic testing alone cannot provide a complete answer; in fact, treatment guided solely by tumor genetics has a 95%+ outcome failure rate.2 Functional testing, on the other hand, is performed in a living system; it can capture the complexities of tumor tissue and biological interactions that take place in the tumor microenvironment2,3 (i.e., the ecosystem that surrounds a tumor inside the body, which includes the immune cells, the extracellular matrix, blood vessels and other cells, like fibroblasts). Functional assays are used to test the effectiveness of anti-cancer therapies directly and can be highly predictive of human drug response.2,3
Think of the tumor as a house, and the microenvironment as its local neighborhood. A tumor and its microenvironment constantly interact and influence each other. [MD Anderson online, 2021]
2.
There are Different Functional Approaches to Precision Oncology
One type of functional test is what scientists call an in vitro screen, where cancer cells are extracted from a biopsied human tumor, grown in a petri dish or glass vial (i.e., artificial environment) in the laboratory, then dosed with anti-cancer therapies to see if the human cancer cells survive.4 Research shows these in-lab tests have high false positive rates5, meaning they are very good at identifying drugs that will not work for an individual, so can be good at ruling out ineffective options.
Another type of functional test is what scientists call a high-throughput virtual in silico screen, a computational biophysics approach to precision oncology. In silico screening tools work in tandem with simulation software and cancer model databases to help predict clinical outcomes.6
Another type of functional test is what scientists call a high-throughput virtual in silico screen, a computational biophysics approach to precision oncology. In silico screening tools work in tandem with simulation software and cancer model databases to help predict clinical outcomes.6
In Vitro Screen
Cancer cells are bathed in a drug for a predefined period in either a glass vial or petri dish, which is not physiologically equivalent to that of a human body.
In Silico Modeling
Biological experiments are conducted on a computer or simulated to make predictions about the behavior of different anti-cancer compounds.7
3.
Personalized In-Life Testing is an Advanced Functional Approach
Personalized in-life testing (or what scientists call an in vivo pharmacology study) is an advanced and clinically relevant form of functional precision oncology.2,3 In cancer research, the gold standard for in vivo functional testing is patient-derived xenografts (PDX)8 — mouse avatars of a person’s cancer developed by engrafting fragments of human tumor tissue into animals.
Research shows that personalized mouse avatars are concordant with human cancer,9 may accurately replicate clinical outcomes and can be used as a translational platform to evaluate next-line treatment strategies.10
4.
YourPDX™ Functional Precision Oncology Can Help Inform Next-Line Treatment Strategies
At Certis, we use personalized orthotopic PDX models of an individual’s cancer for testing. Orthotopic PDX models are different from other types of PDX models. They are developed by engrafting live tumor tissue in the anatomically correct place in mice (e.g., liver to liver or colon to colon) — which has been shown to closely mimic the tumor microenvironment, metastatic behavior and drug response compared to less advanced PDX models.11,12 These avatars of an individual’s cancer allow us to simultaneously test multiple drugs or drug combinations and observe the relative effectiveness of those tested therapies in those personalized mouse avatars.
Tumor Volume Over Time in Response to Multiple Therapeutic Options: By engrafting an individual’s cancer in mice, Certis Oncology can test multiple therapeutic options simultaneously to observe how that individual’s cancer will respond to each potential treatment.
"Individualized medicine for my case was the ideal avenue to pursue...The idea of being treated, while concurrently exploring other feasible options was an ideal scenario. To know that I presently have a drug that is impacting the tumor and potentially four more in reserve is a game changer. I cannot tell you the impact this has had on my family and me. The pioneering work that Certis is doing has hugely impacted my life, knowing that I have a chance to beat back the cancer."
— Jeff Dinkin
What's Next? Be Armed with Therapeutic Options.
YourPDX testing takes an average of 4-6 months to complete and is not intended to inform first-line treatment decisions. At the same time an individual is undergoing prescribed therapy, Certis will develop personalized mouse avatars. Once the mice are fully tumored, these mice are simultaneously tested with a variety of treatment options, indicated by a patient's physician; genomics and AI-enabled predictions may also help inform therapies that are tested. We then evaluate and assess the performance of these tested therapies in orthotopic mouse models to help inform next-line treatment strategies.2,5,10-12 Should a person not respond to first-line treatment, develop resistance to a previously effective therapy, or experience recurrence after successful treatment, the treating oncologist can be armed with alternative therapeutic options for that individual with cancer.
Cancer Treatment Journey (example): A sample timeline illustrating a possible treatment path and possible key outcomes.
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About Us
Certis Oncology Solutions is a life science technology company dedicated to precision oncology and translational science. Our mission is to connect every patient to the right cancer treatment, the first time, every time. Certis explores options for precision therapies beyond the current standard of care and partners with pharmaceutical companies to help develop the next generation of targeted therapeutics. The Certis Laboratory is CLIA-certified (#05D2149049) for high-complexity testing.
YOURPDX IS A FUNCTIONAL TEST THAT MEASURES THERAPEUTIC RESPONSE IN PERSONALIZED PATIENT-DERIVED XENOGRAFT MODELS. TEST RESULTS ARE NOT A REPLACEMENT FOR MEDICAL ADVICE. TREATMENT DECISIONS ARE THE RESPONSIBILITY OF PATIENTS AND THEIR PHYSICIANS. YOURPDX TESTING REQUIRES FRESH TUMOR TISSUE. IT IS ESSENTIAL TO CONTACT US PRIOR TO BIOPSY OR RESECTION SURGERY. TESTIMONIALS APPEARING ON THIS SITE REFLECT REAL-LIFE EXPERIENCES OF THOSE WHO HAVE USED OUR SERVICES.
1 Strobl MAR, West J, Viossat Y et al. Turnover Modulates the Need for a Cost of Resistance in Adaptive Therapy. Cancer Res. 2021;81(4):1135-47. 2 Letai A, Bhola P, Welm A. Functional Precision Oncology: Testing Tumors with Drugs to Identify Vulnerabilities and Novel Combinations. Cancer Cell. 2022;49(1):26-35. 3 Napoli G, Figg WD, Chau C. Functional Drug Screening in the Era of Precision Medicine. Front. Med. 2022;9:912641. 4 Flaherty KT, Gray RJ, NCI-MATCH team et al. Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). J Clin Oncol. Nov. 20, 2020;38(33):3883-3894. 5 Napoli G, Figg WD, Chau C. Functional Drug Screening in the Era of Precision Medicine. Front. Med. 2022;9:912641. 6 Mamrot J et al. Predicting Clinical Outcomes Using Cancer Progression Associated Signatures. Oncotarget. 2021;12(8):845-858. 7 Celebi, R., Bear Don’t Walk, O., Movva, R. et al. In Silico Prediction of Synergistic Anti-Cancer Drug Combinations Using Multi-omics Data. Sci Rep. 2019;9:8949. 8 Jäger W, Xue H, Hayashi T, et al. Patient-Derived Bladder Cancer Xenografts in the Preclinical Development of Novel Targeted Therapies. Oncotarget. 2015;6(25):21522-21532. Wang X, Zhang H, Chen X. 9 Drug Resistance and Combating Drug Resistance in Cancer. Cancer Drug Resist. 2019;2:141-60. 10 Izumchenko, E, Paz, K, Ciznadija, D et al. Patient-Derived Xenografts Effectively Capture Responses to Oncology Therapy in a Heterogeneous Cohort of Patients with Solid Tumors. Annals of Oncology. 2017;28: 2595–2605.11 Walters DM, et al. Clinical, Molecular and Genetic Validation of a Murine Orthotopic Xenograft Model of Pancreatic Adenocarcinoma Using Fresh Human Specimens. PLoS One. 2013;8(10):e77065. 12 Das Thakur M et al. Modeling Vemurafenib Resistance in Melanoma Reveals a Strategy to Forestall Drug Resistance. Nature. 2013;494(7436):251-5.