Match therapy to the type of scar-forming cell in the tumour
The support cells that build a tumour's scaffolding come in several types: some protect the tumour, others restrain it. Treating all of them the same way explains past failures.
Attempts to strip tumour stroma wholesale, notably hyaluronidase in pancreatic cancer and hedgehog inhibition, failed or worsened outcomes, consistent with the finding that some fibroblast subsets restrain tumour growth. Human single-cell and spatial atlases now define myofibroblastic, inflammatory and antigen-presenting fibroblast states. A classifier that assigns patients to stroma-directed treatment by subtype, rather than by disease, is the logical next step.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- Failures are hidden · Negative trials, failed drugs and abandoned programmes are rarely published, so the same mistakes are repeated.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.
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not linked directly; found by shared links- IdeaClear the suppressive neutrophils out of pancreatic tumours first
Shares Desmoplasia (tumour stroma), Single-cell & spatial profiling, Digital pathology & AI, Cold tumours and the immunosuppressive microenvironment.
- IdeaSoften the tissue that new metastases need in order to grow
Shares Erik Sahai, Desmoplasia (tumour stroma), Failures are hidden, Pancreatic ductal adenocarcinoma.
- TechnologyTargeting tumour mechanics and pressure
Shares Desmoplasia (tumour stroma), FAP, Single-cell & spatial profiling, Pancreatic ductal adenocarcinoma.
- IdeaMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours
Shares FAP, Single-cell & spatial profiling, Cold tumours and the immunosuppressive microenvironment, Pancreatic ductal adenocarcinoma.
- IdeaAnchor a TGF-beta trap in the tumour stroma so it cannot act everywhere
Shares Desmoplasia (tumour stroma), FAP, Cold tumours and the immunosuppressive microenvironment, Pancreatic ductal adenocarcinoma.
- IdeaBreak the neutrophil DNA nets that catch tumour cells after surgery
Shares Erik Sahai, Pancreatic ductal adenocarcinoma, Colorectal cancer.
- IdeaBlock the survival signals the tumour's neighbours provide
Shares FAP, Single-cell & spatial profiling, Cold tumours and the immunosuppressive microenvironment.
- IdeaReprogramme suppressive macrophages instead of trying to delete them
Shares Single-cell & spatial profiling, Cold tumours and the immunosuppressive microenvironment, Pancreatic ductal adenocarcinoma, Colorectal cancer.