{ "abstract": "Cancer-associated fibroblasts (CAFs) form a dynamic ecosystem that critically influences tumor progression and therapeutic response. Although recent advances in single-cell and spatial omics have uncovered profound stromal diversity, interpreting the mechanistic relevance of this complexity remains a challenge. Here, we propose a more unifying conceptual framework to bridge high-dimensional data with experimental biology. By categorizing CAFs into conserved molecular phenotypes and distinct spatial archetypes, this model illustrates how CAF identities are intimately linked to local tissue contexts. This refined framework brings the complexity of the tumor stroma into greater focus, underscoring the necessary transition from broad stromal targeting toward precision, context-specific modulation. Ultimately, we hope this integrated effort will aid in the collaborative development of next-generation therapies that selectively target pathogenic stroma in cancer to improve patient outcomes.", "abstract_shown": true, "affiliations": [ "Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA", "Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA", "Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA", "Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, Paris, France; Inserm, U1339, CNRS UMR3666, Paris, France", "Quantitative Biomedical Research Center, Department of Health Data Science and Biostatistics, Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA", "Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK. Electronic address: giulia.biffi@cruk.cam.ac.uk", "Genentech, South San Francisco, CA, USA. Electronic address: krishnamurty.akshay@gene.com", "Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, Paris, France; Inserm, U1339, CNRS UMR3666, Paris, France. Electronic address: fatima.mechta-grigoriou@curie.fr", "Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel. Electronic address: ruth.shouval@weizmann.ac.il", "Cancer Biology & Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: shermam1@mskcc.org", "Amgen Inc., Thousand Oaks, CA, USA. Electronic address: sturle01@amgen.com", "Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: huocong.huang@utsouthwestern.edu" ], "article_type": "review", "arxiv": null, "author_total": 17, "authors": [ { "affs": [ 0 ], "name": "Yunhe Liu" }, { "affs": [ 1 ], "name": "Xiongfeng Chen", "orcid": "0000-0002-7445-3673" }, { "affs": [ 2 ], "name": "Yibo Dai", "orcid": "0009-0007-8023-4665" }, { "affs": [ 1 ], "name": "Yiyue Jia", "orcid": "0009-0006-3906-0272" }, { "affs": [ 3 ], "name": "Yann Kieffer", "orcid": "0000-0003-2722-3071" }, { "affs": [ 4 ], "name": "Luyu Xie", "orcid": "0000-0003-4499-0555" }, { "affs": [ 1 ], "name": "Zhuan Zhou", "orcid": "0000-0002-9683-5760" }, { "affs": [ 1 ], "name": "Lauren A. Tyler", "orcid": "0000-0003-3576-3422" }, { "affs": [ 1 ], "name": "Alex C. Kim", "orcid": "0000-0003-3113-6560" }, { "affs": [ 5 ], "name": "Giulia Biffi", "orcid": "0000-0003-4592-0970" }, { "affs": [ 6 ], "name": "Akshay T. Krishnamurty", "orcid": "0000-0001-5382-1417" }, { "affs": [ 7 ], "name": "Fatima Mechta‐Grigoriou", "orcid": "0000-0002-3751-6989" }, { "affs": [ 8 ], "name": "Ruth Scherz‐Shouval", "orcid": "0000-0002-4570-121X" }, { "affs": [ 9 ], "name": "Mara H. Sherman", "orcid": "0000-0001-7826-3888" }, { "affs": [ 10 ], "name": "Shannon J. Turley", "orcid": "0000-0002-0444-3031" }, { "name": "Linghua Wang", "orcid": "0000-0001-9380-0266" }, { "affs": [ 11 ], "name": "Huocong Huang", "orcid": "0000-0002-6345-4566" } ], "bibtex": "https://research.draconitic.com/paper/f573h37hbqbkv.bib", "cited_by": 19, "doi": "10.1016/j.ccell.2026.06.001", "fulltext_url": null, "id": "f573h37hbqbkv", "issns": [ "1535-6108", "1878-3686" ], "landing_url": "https://doi.org/10.1016/j.ccell.2026.06.001", "language": "en", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "1312|Single-cell and spatial transcriptomics" ] ], "openalex": "W7165935107", "pdf_url": null, "pmcid": "PMC13383123", "pmid": "42349429", "published": "2026-06-25", "publisher": "Cell Press", "ris": "https://research.draconitic.com/paper/f573h37hbqbkv.ris", "sources": [ { "first_seen": "2026-10-30T13:26:46Z", "native_id": "W7165935107", "source": "openalex", "url": "https://doi.org/10.1016/j.ccell.2026.06.001" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Single-cell and spatial transcriptomics", "subfield": "molecular-biology" } ], "title": "Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts", "title_text": "Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts", "type": "peer-reviewed", "updated_at": "2026-11-09T13:21:05Z", "url": "https://research.draconitic.com/paper/f573h37hbqbkv", "venue": "Cancer Cell", "versions": [] }