PDAC

PDAC Validated Solution

 

A defined 3D PDAC tumor-CAF co-culture workflow for studying tumor-stroma interactions, CAF-mediated chemoprotection, and therapeutic response.


The PDAC Validated Solution combines pancreatic cancer cells with primary PDAC CAFs in a defined 3D matrix environment, enabling researchers to evaluate how stromal biology alters drug response across PANC-1 and AsPC-1 model contexts.

Model at a glance

The RASTRUM PDAC Validated Solution recreates tumor-stroma interactions by combining pancreatic cancer cells with cancer-associated fibroblasts in a defined 3D matrix environment. To capture broad coverage of key PDAC signaling pathways, the workflow includes either PANC-1 or AsPC-1 cancer cells paired with primary PDAC CAFs , enabling comparison of drug efficacy across primary and metastatic contexts.

  • Disease Area: Pancreatic cancer / PDAC

  • Model type: 3D tumor-CAF co-culture

  • Cancer cell contexts: PANC-1 and AsPC-1

  • Stromal component: Primary PDAC CAFs

  • Research focus: Tumor-stroma crosstalk, chemoprotection, therapeutic response

  • Readouts: Viability, live/dead imaging, brightfield imaging, drug response, optional RNA preparation

  • Reference compounds: Gemcitabine, paclitaxel, galunisertib

What this workflow helps you investigate

Functional Validation- Drug Response

Proof point: CAF co-culture alters therapeutic response in 3D PDAC models

In co-culture models, CAF interactions increased resistance to paclitaxel relative to monoculture conditions. Addition of galunisertib reversed the chemoprotective effect, supporting use of the workflow for evaluating combination strategies targeting stromal-mediated resistance.

This workflow is designed for teams studying:

 

  • PDAC tumor microenvironment biology
  • Stromal contributions to drug resistance
  • CAF-mediated chemoprotection
  • Tumor-stroma signaling across PANC-1 and AsPC-1 contexts
  • Pathway-targeted or combination therapy strategies
  • Scalable 3D drug response workflows
PDAC_data_pack_Fig4_padded

Context of use

This validated workflow is designed for researchers who need a reproducible 3D PDAC tumor-stroma model for therapeutic response studies in a defined context of use.

  • Evaluate therapeutic efficacy in the presence of tumor-stroma crosstalk
  • Investigate stromal contributions to tumor progression and drug resistance
  • Identify targetable resistance mechanisms in the tumor microenvironment
  • Screen pathway-targeted therapies and combination treatments

 

Image depicts immunofluorescence assessment of cancer cell–CAF interactions in RASTRUM optimized models. Positive immunofluorescence staining for pan cytokeratin (cancer cell marker, green) alongside phalloidin staining for actin filaments (red) after 7 days in culture. (A) PANC-1/CAF and (B) AsPC-1/CAF co-cultures. 

What this model demonstrates

The PDAC Validated Solution is designed to generate interpretable, decision-grade insights in defined PDAC tumor-stroma contexts.

  • Stromal signaling is context-dependent
    Distinct pathway enrichment profiles between PANC-1 and AsPC-1 highlight how tumor genotype shapes tumor-stroma crosstalk and downstream resistance mechanisms.

  • CAF co-culture drives chemoprotection
    AsPC-1 cells co-cultured with CAFs demonstrate reduced chemotherapy sensitivity, consistent with stromal-mediated protection.

  • The model supports combination therapy screening
    The workflow can be used to evaluate therapeutic strategies that counteract CAF-mediated drug resistance or remain effective in the presence of tumor-stroma signaling.

Molecular Characterization

Molecular characterization

RNA-seq reveals pathway activation associated with tumor-stroma signaling


Differential gene expression analysis highlights pathway enrichment related to fibroblast activation, pro-tumourigenic processes, and therapeutic resistance. Distinct pathway profiles between PANC-1 and AsPC-1 co-cultures support the use of this workflow in biologically rich PDAC contexts.



Functional Validation- Drug Response

Functional validation

Tumor-stroma interactions alter therapeutic response


Co-culture models demonstrate increased resistance to paclitaxel relative to monoculture conditions, consistent with stromal-mediated chemoprotective effects observed in PDAC. Addition of the TGFBR1 inhibitor galunisertib reverses the chemoprotective effect in co-cultures, supporting use of this model for combination therapy evaluation.  



Key workflow specifications

Defined model parameters support reproducible execution across runs and downstream analyses.

  • Model format: Imaging Model

  • Matrix: Px03.84 (~3 kPa, RGD, YIGSR, GFOGER, HA, full-length fibronectin)

  • Cell density: Cancer cells 2M/mL; CAFs 10M/mL

  • Co-culture ratio: 1:5 tumor:CAF

  • Drug treatment: Day 4 post-print, 72 hr exposure

  • Reference compounds: Gemcitabine, paclitaxel, galunisertib

  • Downstream analyses: Viability assessment, live/dead and brightfield imaging, drug screening, optional RNA preparation for sequencing

Get the PDAC model package

FAQs
What is the RASTRUM PDAC Validated Solution?
The RASTRUM PDAC Validated Solution is a 3D pancreatic ductal adenocarcinoma workflow designed to model tumor-stroma interactions using pancreatic cancer cells and cancer-associated fibroblasts in a defined RASTRUM matrix environment. It supports research into therapeutic response, stromal signaling, and combination screening.
What cell types are used in the RASTRUM PDAC Validated Solution?
The RASTRUM PDAC Validated Solution uses a 3D tumor-CAF co-culture with pancreatic cancer cells such as PANC-1 or AsPC-1 paired with primary PDAC cancer-associated fibroblasts. Exact cell types, ratios, matrix, and treatment conditions are defined in the selected workflow materials.
How does the PDAC Validated Solution model tumor-stroma interactions?
The PDAC Validated Solution uses a 3D co-culture format to place pancreatic cancer cells and cancer-associated fibroblasts in a matrix environment where tumor-stroma crosstalk can be studied. This can support research into stromal signaling, response modulation, resistance mechanisms, and combination therapy strategies.
How does the PDAC Validated Solution support combination therapy screening?
The PDAC workflow can support treatment-response and combination-therapy studies using a reproducible tumor-CAF 3D model with defined treatment timing and readouts. Example reference compounds for the PDAC workflow include gemcitabine, paclitaxel, and galunisertib. Suitability should be evaluated within the defined PDAC context of use and selected readouts.
What readouts are used in the PDAC Validated Solution?
Readouts for the PDAC Validated Solution include drug response using CellTiter-Glo 3D, live/dead staining, brightfield imaging, and RNA isolation and preparation for RNA-seq. Readouts should be selected based on the Protocol Pack, Data Pack, and research question.
Can Discovery Services support oncology and tumor microenvironment models?
Discovery Services can support oncology and tumor microenvironment model development, including tumor-stroma co-culture, CAF biology, dense tumor biology, treatment response, and custom context-of-use studies. Disease areas may include PDAC, colorectal cancer, ovarian, breast, and lung cancer, depending on project feasibility.