# Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer

Source: https://onco.cc/key-papers/paper-olive-hedgehog-stroma-gemcitabine-delivery-science-2009/  
OnCo record `paper-olive-hedgehog-stroma-gemcitabine-delivery-science-2009` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Pancreatic tumours in mice, like those in people, have so few blood vessels that chemotherapy barely reaches them; stripping away the surrounding scar tissue with a hedgehog-blocking drug let more gemcitabine in and held the disease still for a while.

## Summary

A mouse model of pancreatic ductal adenocarcinoma refractory to gemcitabine was studied; tumours were poorly perfused and poorly vascularised, properties shared with human disease. Co-administration of IPI-926, which depletes tumour-associated stroma by inhibiting hedgehog signalling, produced a transient increase in intratumoural vascular density and gemcitabine concentration, leading to transient stabilisation of disease. Inefficient drug delivery may therefore be an important contributor to chemoresistance.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Science
- Year: 2009
- DOI: 10.1126/science.1171362
- Authors: Olive KP, Jacobetz MA, Davidson CJ, et al.
- Findings: Mouse and human pancreatic tumours are poorly perfused and vascularised.; Hedgehog inhibition transiently raised vascular density and intratumoural gemcitabine and stabilised disease.
- What it means: It launched a decade of attempts to strip the stroma to let drugs in; the clinical trials that followed failed, and later mouse work showed the stroma also restrains the tumour.
- Caveats: Mouse model, transient effect.; Hedgehog inhibitors were harmful or futile in patients (Rhim 2014, Ozdemir 2014).

## Sources

- Olive et al., Science 2009: hedgehog inhibition improves gemcitabine delivery in the mouse model: https://doi.org/10.1126/science.1171362
- PubMed: https://pubmed.ncbi.nlm.nih.gov/19460966/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Gemcitabine](https://onco.cc/drugs/gemcitabine/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Hedgehog signalling](https://onco.cc/pathways/hedgehog/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/)
- people: [David A. Tuveson](https://onco.cc/people/david-tuveson/)
- journals: [Science](https://onco.cc/journals/science/)

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