When Genomics Says "Maybe" — Get a Definitive Answer

Validate actionable variants with functional drug testing on patient-derived organoids

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The VUS Dilemma

Genomic sequencing has transformed oncology — but it doesn't always give clear answers.

When your patient's tumor harbors a Variant of Uncertain Significance, you face a difficult clinical decision:

  • The variant is uncharacterized — not enough functional data exists to classify it as pathogenic or benign
  • Published evidence is limited — the specific alteration hasn't been studied in clinical trials
  • Off-label therapy is hard to justify — without evidence, insurance may deny coverage and patients bear risk
  • Patients may miss effective options — or receive ineffective ones based on incomplete information

The clinical reality: Up to 40% of variants identified by tumor sequencing are classified as VUS. Many of these are in genes with targetable therapies — but without functional validation, their clinical significance remains unknown.

Functional Validation for Uncertain Variants

Don't guess. Test.

OncoForma provides a direct answer to the VUS question by testing drug response on your patient's actual tumor cells.

1

Grow Organoids

We culture patient-derived organoids from tumor tissue, preserving the genetic alterations and cellular behavior of the original cancer

2

Test Targeted Inhibitors

Screen against 10-30 drugs targeted to the variant class — including approved therapies, off-label options, and investigational agents

3

Measure Actual Response

Quantify drug sensitivity with dose-response curves and IC50 values — not predictions, but measured outcomes

4

Report in 21 Days

Receive clinician-ready results fast enough to inform treatment decisions

Genomics asks the question. We answer it.

Laboratory drug sensitivity testing

Example: Uncharacterized ERBB2 Alteration

Clinical Scenario

A 58-year-old patient with metastatic colorectal cancer undergoes comprehensive genomic profiling. The report identifies an ERBB2 (HER2) missense variant — but it's classified as a VUS.

The oncologist faces a dilemma: HER2-targeted therapies like tucatinib or neratinib could be effective, but without evidence that this specific variant confers sensitivity, the treatment decision is uncertain.

OncoForma Testing

The patient's tumor sample is used to generate organoids. OncoForma tests the organoids against a panel of HER2-targeted agents:

  • Tucatinib
  • Neratinib
  • Lapatinib
  • Trastuzumab deruxtecan (T-DXd)
  • Pertuzumab + trastuzumab

Results

The organoids show marked sensitivity to tucatinib (IC50 well below clinically achievable concentrations) and moderate sensitivity to neratinib. Standard chemotherapy agents show minimal effect.

Clinical implication: Functional evidence supports the use of HER2-targeted therapy for this patient, providing documentation to support treatment decisions and insurance appeals.

Note: This is a representative scenario. Actual results vary by patient and tumor biology.

The Case for Functional Testing

Organoid drug testing is supported by peer-reviewed clinical evidence demonstrating correlation between in vitro response and patient outcomes.

Vlachogiannis et al. (2018)

In a prospective study of metastatic colorectal and gastroesophageal cancer patients, organoid drug responses predicted patient clinical response with 88% sensitivity and 100% specificity.

Read the study in Science →

Ooft et al. (2019)

Patient-derived organoids predicted clinical response to irinotecan-based chemotherapy in metastatic colorectal cancer with 80% accuracy, outperforming genomic biomarkers alone.

Read the study in Science Translational Medicine →

Driehuis et al. (2019)

Comprehensive review demonstrating that organoids maintain the genetic and phenotypic characteristics of patient tumors, making them reliable models for drug sensitivity testing and precision medicine applications.

Read the review in Nature Protocols →

Why functional testing matters for VUS: When a variant lacks published functional characterization, testing drugs directly on patient-derived organoids provides empirical evidence of drug sensitivity — filling the gap that genomics alone cannot address.

Have a Patient with an Uncertain Variant?

Let's discuss whether functional testing can help guide the treatment decision.

Contact Us

Or email us directly at info@oncoforma.com

What to Include in Your Inquiry

  • Cancer type and stage
  • Variant(s) of interest and gene(s) involved
  • Current or prior treatments
  • Timeline for treatment decision
  • Sample availability (fresh tissue, biopsy planned, etc.)

Learn More

How It Works

Technical overview of our organoid platform and drug testing methodology

Clinical Evidence

Published validation studies and outcomes data

Order a Test

Sample requirements, shipping, and turnaround time