Targeting tumour mechanics and pressure
Stiff, high-pressure tumours squeeze their own blood vessels shut, keeping drugs out. Softening them is a way in.
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.
How it works
Reducing extracellular matrix content or stiffness lowers solid stress, decompresses vessels, and improves delivery of drugs and immune cells.
- Addresses a delivery barrier shared by the deadliest tumours
- Cheap existing agents to test
- Measurable with imaging
- PEGPH20 phase 3 failure
- Loosening the matrix may aid invasion
- No demonstrated effect on outcomes
Latest papers
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