# Targeting tumour mechanics and pressure

Source: https://onco.cc/technologies/mechanobiology-therapy/  
OnCo record `mechanobiology-therapy` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Stiff, high-pressure tumours squeeze their own blood vessels shut, keeping drugs out. Softening them is a way in.

## Summary

Desmoplastic tumours such as pancreatic cancer generate solid stress that collapses vessels; agents that reduce matrix stiffness (losartan, hyaluronidase, LOXL2 inhibitors) aim to reopen perfusion. PEGPH20, the furthest-advanced hyaluronidase, failed its phase 3 in pancreatic cancer, and losartan combinations remain investigational. The physics is well characterised; converting it into benefit has so far failed.

## Fields

- Kind: Technology
- Status: preclinical
- Last checked: 2026-09-08
- Tags: frontier
- Principle: Reducing extracellular matrix content or stiffness lowers solid stress, decompresses vessels, and improves delivery of drugs and immune cells.
- Strengths: Addresses a delivery barrier shared by the tumours with the lowest survival; Cheap existing agents to test; Measurable with imaging
- Limitations: PEGPH20 phase 3 failure; Loosening the matrix may aid invasion; No demonstrated effect on outcomes

## Sources

- ClinicalTrials.gov: losartan pancreatic cancer: https://clinicaltrials.gov/search?term=losartan%20pancreatic%20cancer

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- targets: [FAP](https://onco.cc/targets/fap/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/)
- roadmaps: [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Invasion: proteases, adhesion & the invasive front](https://onco.cc/pathways/invasion-ecm-degradation/)

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