# Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma

Source: https://onco.cc/key-papers/paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014/  
OnCo record `paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Removing the hedgehog signal that builds the scar tissue around pancreatic tumours in mice gave less stroma but more aggressive, more vascular cancers, and only anti-angiogenic treatment helped them.

## Summary

Sonic hedgehog, overexpressed by neoplastic cells and driving a fibroblast-rich desmoplastic stroma, was deleted in a mouse model of pancreatic ductal adenocarcinoma. Shh-deficient tumours had reduced stromal content but were more aggressive, undifferentiated, more vascular and more proliferative, effects fully recapitulated by a smoothened inhibitor in control mice. VEGFR blockade selectively improved survival of Shh-deficient tumours, indicating that hedgehog-driven stroma suppresses tumour growth partly by restraining angiogenesis.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Cancer Cell
- Year: 2014
- DOI: 10.1016/j.ccr.2014.04.021
- Authors: Rhim AD, Oberstein PE, Thomas DH, et al.
- Findings: Hedgehog deletion or smoothened inhibition reduced stroma but produced more aggressive, vascular tumours.; VEGFR blockade selectively helped stroma-depleted tumours.
- What it means: Published alongside Ozdemir, it explains why the hedgehog inhibitor trials in patients failed and why stromal targets are now chosen for their signalling rather than their bulk.
- Caveats: Mouse genetics and models.; Does not exclude benefit from selective stromal reprogramming.

## Sources

- Rhim et al., Cancer Cell 2014: stromal elements restrain pancreatic cancer: https://doi.org/10.1016/j.ccr.2014.04.021
- PubMed: https://pubmed.ncbi.nlm.nih.gov/24856585/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- institutions: [Herbert Irving Comprehensive Cancer Center, Columbia University](https://onco.cc/institutions/columbia-hicc/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Hedgehog signalling](https://onco.cc/pathways/hedgehog/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/)
- journals: [Cancer Cell](https://onco.cc/journals/cancer-cell/)

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