SCIENCE
The Science of Functional Tumor Profiling
Functional chemosensitivity: measuring drug response in living tumor tissue
THE PLATFORM
The SAGE Oncotest™ is a 3D functional assay
Most drug sensitivity assays dissociate tumor cells into single-cell monolayers. That step destroys cell–cell contacts, extracellular matrix, and the tumor microenvironment — the structural context that governs drug penetration and resistance in living tissue.
The SAGE Oncotest™ preserves three-dimensional tumor architecture directly from the patient's biopsy. Cells remain in their native spatial organization through the entire testing process, maintaining the biological signals that determine real-world drug sensitivity.
Hirschhaeuser et al., J Biotechnol 2010 • Maestri et al., ASCO 2024 • SAGE Patent US10,564,100
→ Read more: 3D microtumors
3D ARCHITECTURE PRESERVES
TME
Tumor microenvironment, cell–cell contacts, and extracellular matrix — all lost in conventional 2D monolayer dissociation
RESULTS FROM FRESH PATIENT TISSUE
7–10 days
Direct biopsy to actionable drug sensitivity data — without organoid expansion delays
RESISTANCE DIVERGENCE
Drug sensitivity profiles differ significantly between matched primary and metastatic specimens from the same patient — profiling one does not predict the other
Primary ≠ Met
TUMOR HETEROGENEITY
The SAGE Oncotest™ reflects the tumor heterogeneity of the patient's biopsy
Drug sensitivity profiles diverge significantly between matched primary and metastatic specimens from the same patient. Acquired resistance and site-specific sensitivity shifts develop across the treatment course — and are invisible to a single primary-tumor profile.
The SAGE Oncotest™ can profile primary and metastatic specimens sequentially, capturing the resistance landscape as it exists at the time treatment decisions are being made.
Nitiyanandan et al., AACR 2025
→ Read more: tumor heterogeneity
ASSAY DESIGN
The only assay measuring both cytotoxicity and antiproliferation
Cytocidal agents (chemotherapy)
Kill tumor cells directly. Detected by cytotoxicity readout.
CDK4/6 inhibitors, EGFR inhibitors, HER2-targeted agents, PI3K/mTOR inhibitors, and BRAF/MEK inhibitors cause growth arrest without cell death. A cell-death readout alone produces false negatives for every one of them — which together account for a substantial portion of all targeted therapy prescriptions.
Cytostatic agents (most targeted therapies)
Halt proliferation without killing cells. Missed entirely by cytotoxicity-only assays.
The SAGE Oncotest™ measures cytotoxicity and antiproliferation simultaneously on the same specimen. This is the only assay that captures both cytocidal and cytostatic drug effects — a prerequisite for faithfully evaluating the full range of modern chemotherapy and targeted agents.
SAGE Oncotest™ — dual readout
Cytotoxicity + antiproliferation measured simultaneously. Both mechanisms captured on the same specimen.
Cytotoxicity + antiproliferation measured simultaneously. Both mechanisms captured on the same specimen.
Maestri et al., AACR 2025 • Garewal et al., JNCI 1986
→ Read more: dual readout assay
HISTORICAL CONTEXT
The barrier to adoption was feasibility, not scientific validity
CLONOGENIC ASSAY ACCURACY (54 TRIALS, 35 INSTITUTIONS)
91%
Accuracy for drug resistance prediction across 2,300 patients — the scientific validity was established decades ago
Clonogenic assays from the 1970s–1990s predicted drug resistance with 91% accuracy across 2,300 patients and 54 trials from 35 institutions. The science was never the problem.
Von Hoff, JNCI 1990 • Von Hoff, NEJM 1983
→ Read more: SAGE vs. prior assays
The barrier was clinical: fewer than 28% of tumors formed adequate colonies, and a 133-patient trial took 4.5 years to complete. Organoids face the same race-with-the-patient problem — weeks to months for expansion, often too late for the next treatment decision.
The SAGE Oncotest™ solves the feasibility problem: results from fresh patient tissue in 7–10 days, no expansion required.
TUMOR GROWTH RATE (CLONOGENIC ASSAY)
<28%
Fewer than 28% of tumors formed adequate colonies — feasibility, not science, was the limiting factor
Explore this section
3D microtumors
TME preservation, native architecture, and drug response fidelity in patient tissue
Read more →
SAGE vs. prior assays
From clonogenic assays to organoids: why feasibility was the barrier, not science
Read more →
Tumor heterogeneity
Primary vs. metastatic resistance divergence and SAGE sequential profiling
Read more →
Dual readout assay
Why measuring cytotoxicity alone misses the most-prescribed targeted agents
Read more →
References
1. Hirschhaeuser F, et al. Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol. 2010;148(1):3-15. doi:10.1016/j.jbiotec.2010.01.012
2. Maestri C, et al. 3D cell cultures exhibit increased drug resistance, particularly to taxanes. J Clin Oncol. 2024;42(16_suppl):e12599.
3. Maestri C, et al. A novel viability and proliferation assay to enhance precision oncology. Cancer Res. 2025;85(5_Suppl):A004.
4. Nitiyanandan R, et al. Abstract A016: Heterogeneity of drug sensitivity profiles of primary and metastatic tumors. AACR Special Conference. Boston, MA, March 2025.
5. Garewal HS, et al. ATP assay: ability to distinguish cytostatic from cytocidal anticancer drug effects. JNCI. 1986;77:1039-1045.
6. Von Hoff DD. He's not going to talk about in vitro predictive assays again, is he? J Natl Cancer Inst. 1990;82(2):96-101.
7. Von Hoff DD. Send this patient's tumor for culture and sensitivity. N Engl J Med. 1983;308(3):154-155.
8. SageMedic Corp. Three-dimensional tumor culture system and methods. US Patent 10,564,100.