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www.indivumed.com/approach/target-validation/
An open incubator showing the patient-derived cell-cultures used in target validation for precision oncology drug discovery.

In-depth target validation

Studying a target’s impact on specific cancer patient populations with a wide variety of biochemical and phenotypic assays.


Target Validation Locking onto the right target

We thoroughly validate the targets emerging from our in-silico discovery pipeline. Beyond standard 2D cell lines, we emphasize the use of patient-derived 3D tumor models that better reflect the disease biology. These models are created from the same tumor material on which the multi-omics data for target ID is based. This allows validation to be performed in an environment that is as close to the patient as possible, de-risking subsequent therapeutic development.

Two masked researchers fill pipettes with liquid, working with high-quality tumor samples crucial for cancer drug discovery.

Patient-derived tumor modelsHigh-quality tissue samples are foundational to cancer drug discovery.

An important asset that sets us apart is the exceptional quality and standardization of our tumor sample biobank. By adhering to a rapid collection protocol and optimized storage standards, we safeguard the integrity of a tumor as much as possible.

Crucially, above and beyond facilitating high-quality data, we generate 2D and 3D cellular models from this tissue, that we use for target validation. Just like the data obtained from these samples reflect cancer closer to physiological conditions, our in-house-generated, patient-derived tumor models are excellent representations of the characteristic features of the disease.

Validation processA comprehensive target validation process

Guided by multi-omics and clinical data, we start by selecting appropriate, patient-derived 2D and 3D cellular models and combine them with commercial cell lines to create a disease model panel. Various state-of-the-art genetic and biochemical techniques are then applied to assess the target’s role in tumor growth.

Disease model development

  • Patient-derived and commercial
  • 2D, spheroid and organoid cellular models
  • Preselection based on omics and clinical data

Genetic approach

  • CRISPR interference
  • CRISPR knockout
  • siRNA knockdown

Functional readouts

  • Viability
  • Spheroid formation
  • Migration
  • Invasion
  • Additional context-specific functional assay development

Patient-derived cell cultures result in models that closely represent tumor biology.

Characterization processTarget characterization and screening assay establishment

Alongside target validation, we perform further biochemical and biological characterization. Our experts examine the protein class and structure, subcellular location, and other biological parameters of the target. This enables the establishment of proof-of-concept cell-free and cell-based assays for ligand screening and validation.

Cell-free assays

  • Target expression and purification
  • Functional enzymatic assay design
  • Assay optimization for HTS

Cell-based assays

  • Gene expression
  • Gene splicing
  • Protein folding and secretion
  • Rescue and mutant experiments
  • Assay optimization for HTS

Target tissue biobank capabilities

  • Single and multiplex IHC
  • Spatial transcriptomics expression analysis
  • Gene expression by RT-PCR