Functional Precision Medicine: Rewriting the Rules in the Fight Against Glioblastoma

Moving beyond genetic blueprints to actual treatment response testing

Glioblastoma Precision Medicine Oncology

The Unthinkable Choice

Imagine sitting in a neuro-oncologist's office, hearing the words "glioblastoma" and "median survival of 12-18 months." Then comes an even more devastating choice: which toxic chemotherapy regimen to pursue, with your doctor honestly admitting that it's essentially a guessing game. For the approximately 300,000 people worldwide diagnosed each year with glioblastoma, the most aggressive and lethal primary brain tumor in adults, this terrifying scenario is reality 1 8 .

Current Challenge

The addition of temozolomide to standard therapy extends life by just 2.5 months on average 9 .

New Hope

Functional precision medicine (FPM) represents a revolutionary approach that's beginning to transform glioblastoma treatment.

Beyond the Genetic Blueprint: Why Glioblastoma Defies Conventional Treatment

Limitations of Genetics-Only Approaches
  • Cellular diversity within tumors 8
  • Blood-brain barrier prevents drug delivery 1 9
  • Glioblastoma stem cell resistance 1 9
  • Failed targeted therapy approaches 4 6
What is Functional Precision Medicine?

FPM tests how live cancer cells respond to drugs directly—moving from predicting response to actually observing it 7 .

1. Tumor Collection
Collecting tissue during surgery
2. Cell Culture
Processing and culturing cells in laboratory
3. Drug Testing
Exposing cells to multiple treatments
4. Response Measurement
Identifying effective treatments
5. Treatment Selection
Guiding patient-specific therapy

A Closer Look: The Regorafenib Sensitivity Experiment

A groundbreaking study published in 2025 exemplifies the power of functional precision medicine in tackling recurrent glioblastoma 3 .

Methodology: Step-by-Step
26 Tumor Samples
From 18 patients
3D Organoids
GBM-EXPs created
Drug Testing
Two chemotherapy drugs
Clinical Correlation
16 patients studied

Results and Analysis

Drug Sensitivity Profiles in Glioblastoma Organoids
Drug Sensitive Tumors Resistant Tumors
Temozolomide 35% 65%
Regorafenib 77% 23%
Clinical Outcomes Based on Functional Testing

77%

Tumors sensitive to regorafenib

7.5

Months progression-free survival (sensitive tumors)

3.6

Months progression-free survival (resistant tumors)

The Scientist's Toolkit: Key Technologies Powering the Functional Medicine Revolution

3D Organoids

Patient-derived models maintaining tumor complexity and microenvironment 3 8 .

Drug Screening

High-throughput platforms testing multiple drugs simultaneously 4 .

Biomarkers

BH3 profiling, NAD(P)H FLIM, and ATP quantification 3 4 5 .

Machine Learning

GAVA tool integrating genetic and functional data 5 .

Beyond the Lab: The Expanding Frontier of Functional Precision Medicine

ATTRACT Trial

Randomized Phase 2 study with 240 patients across five Austrian centers, testing FPM in newly diagnosed glioblastoma 4 .

Ongoing
Combination Therapies

UCLA researchers identified ABBV-155 with BCL-XL targeting, producing tumor shrinkage in preclinical models 5 .

Preclinical Success
Blood-Brain Barrier

Innovative methods including focused ultrasound, intra-arterial infusion, and convection-enhanced delivery 1 .

Delivery Solutions

"Many cancer treatments are based on the genetic profile of a patient's tumor. However, genomic features alone can't always predict how a tumor will respond to a therapy. This study explores a new approach that looks beyond the tumor's genetic blueprint."

Dr. David Nathanson of UCLA

A New Horizon in Neuro-Oncology

Functional precision medicine represents more than just another incremental advance in glioblastoma treatment—it constitutes a fundamental rethinking of how we match patients with therapies. By complementing genetic information with direct observation of treatment responses, FPM offers a more complete picture of tumor behavior and vulnerability.

Current Challenges
  • Standardizing protocols across institutions
  • Reducing turnaround times
  • Securing insurance coverage
Future Opportunities
  • Multiple clinical trials underway
  • Rapidly advancing technologies
  • Personalized treatment strategies

For the first time in decades, neuro-oncologists may soon have more to offer their patients than difficult choices and guarded prognoses—replacing them with data-driven treatment plans and genuine hope.

References