# Soften the tissue that new metastases need in order to grow

Source: https://onco.cc/ideas/idea-bio2-matrix-stiffness-prevention/  
OnCo record `idea-bio2-matrix-stiffness-prevention` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cancer cells need stiff, cross-linked tissue scaffolding to settle and grow in a new organ. Blocking the enzymes that build it may stop new colonies taking hold.

## Summary

LOX and LOXL2 cross-link collagen to create the stiff matrix required for metastatic outgrowth, and hypoxia-driven LOX secretion prepares bone and lung niches. An anti-LOXL2 antibody failed in fibrosis and in advanced pancreatic cancer, but was never tested in the prevention setting where the biology predicts benefit and the target burden is small.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: LOX or LOXL2 inhibition given adjuvantly, when only micrometastatic disease is present, delays radiographic metastasis, while having no effect on established macroscopic disease.
- Rationale: Matrix cross-linking is rate-limiting for outgrowth, not for the survival of an already vascularised lesion, which would explain why treatment trials failed. Early-intervention-only benefit has precedent in anti-fibrotic therapy for lung fibrosis.
- Proposed test: Test the setting-dependence in mice first: the identical agent in adjuvant versus established-metastasis designs. Only a large adjuvant-specific effect should trigger a human trial in high-risk resected disease.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019): https://doi.org/10.1002/cam4.2474

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- pathways: [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [VHL / HIF oxygen sensing](https://onco.cc/pathways/hif-vhl/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/)
- people: [Erik Sahai](https://onco.cc/people/erik-sahai/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/)
- key papers: [Are 90% of deaths from cancer caused by metastases?](https://onco.cc/key-papers/paper-dillekas-cancer-med/)

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