# Block the survival signals the tumour's neighbours provide

Source: https://onco.cc/ideas/idea-bio1-stromal-resistance-blockade/  
OnCo record `idea-bio1-stromal-resistance-blockade` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cancer cells can survive a drug because surrounding normal cells feed them growth signals. Blocking those signals could make existing drugs work better and longer.

## Summary

Fibroblast- and macrophage-derived factors including HGF, FGFs and neuregulin rescue tumour cells from targeted therapy in co-culture and in vivo, an effect largely invisible in monoculture screens. Environment-mediated resistance argues for combining targeted agents with blockade of the specific rescuing ligand or its receptor, selected by profiling the tumour's own stroma rather than the tumour cells alone.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Stroma-directed ligand blockade added to targeted therapy deepens response in tumours whose stroma expresses the rescuing ligand, and stromal ligand expression predicts which patients benefit.
- Rationale: The rescue phenomenon was demonstrated systematically in large co-culture screens; the clinical failure of some combination trials may reflect unselected populations rather than a wrong mechanism.
- Proposed test: Score stromal ligand expression on baseline biopsies from a completed combination trial to test the predictive hypothesis retrospectively before designing a selected prospective study.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- technologies: [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- targets: [FAP](https://onco.cc/targets/fap/), [HER3](https://onco.cc/targets/her3/), [MET](https://onco.cc/targets/met/)
- drugs: [Patritumab deruxtecan](https://onco.cc/drugs/patritumab-deruxtecan/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/)

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