{"entity":{"id":"idea-bio2-caf-subtype-assignment","kind":"idea","name":"Match therapy to the type of scar-forming cell in the tumour","aka":[],"tldr":"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.","summary":"Attempts to strip tumour stroma wholesale, including 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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal"],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai","rna-seq"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia","cms-subtypes"],"trials":[],"people":["erik-sahai"],"bottlenecks":["b-tme-immunosuppression","b-negative-results","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A validated fibroblast-subtype classifier predicts which patients benefit from stroma-directed therapy, and pooling all subtypes together dilutes an effect that exists only in the myofibroblastic-dominant subgroup.","rationale":"Hedgehog inhibition accelerated pancreatic cancer in mice by depleting restraining stroma, a clear demonstration that stromal identity determines direction of effect. Subtype-guided assignment turned negative results into positive ones in breast cancer and in colorectal consensus subtypes.","test":"Reanalyse tissue from failed stroma-targeting trials by fibroblast subtype for a retrospective interaction test; if positive, run a prospective subtype-selected trial.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":7},"route":"/ideas/idea-bio2-caf-subtype-assignment/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"target":[{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"}],"term":[{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"},{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"}],"person":[{"id":"erik-sahai","kind":"person","name":"Erik Sahai","route":"/people/erik-sahai/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}