---
title: "Fact sheet: HUB Organoids as translational avatars for KRAS research"
description: Uncover how PDOs enable insights into resistance and support combination strategy development across KRAS-mutant cancers
---

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# Patient-derived organoids as translational avatars for KRAS research

### Learn how PDOs support lead identification and modelling resistance mechanism

**More than 25 experts in targeted oncology have downloaded this case study**

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## A closer look at challenges in KRASi development

![section-img2](https://resources.huborganoids.nl/hs-fs/hubfs/assets2024/kras-pink-teal.png?width=483&name=kras-pink-teal.png)

Despite advances with KRAS-targeted therapies, resistance remains a major challenge as tumors adapt through secondary mutations and pathway reactivation. Our PDO platform models both intrinsic and acquired resistance in a mutation- and tissue-specific context, preserving patient-derived molecular and phenotypic features for translationally relevant drug evaluation.

Using our CRC-derived PDO biobank, we tested MRTX1133, a selective KRAS-G12D inhibitor, and observed substantial heterogeneity, with some models showing sensitivity and others no response despite sharing the same mutation. By integrating multi-omics profiling, including single-cell RNA sequencing, our platform enables stratification of responders, identification of biomarkers, and design of rational drug combinations to guide therapy selection and indication expansion.

## What you'll learn:

- Our protocol for modelling drug-tolerant and acquired-resistant states by stepwise drug exposure
- Comparative sensitivity profiles of KRAS-mutant PDOs to available G12C and G12D inhibitors
- Functional heterogeneity within and across KRAS mutation classes
- Preclinical data supporting KRAS/EGFR combination strategies
- Use of single-cell RNA sequencing to map resistance programs and discover biomarkers of response

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## Now enrolling for Pan-KRAS PDO Screen

Benchmark your inhibitor against daraxonrasib and get patient-relevant preclinical evidence.

 

[book a consultation](https://www.huborganoids.nl/kras-inhibitor-testing-organoid-solutions)

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