OnCo
ideasIdea

Soften the tissue that new metastases need in order to grow

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.

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.

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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
8
Bottlenecks it attacks

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