The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity
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- dc.contributor.author Sibai, Mustafa
- dc.contributor.author Cervilla García, Sergi
- dc.contributor.author Grases, Daniela
- dc.contributor.author Musulen, Eva
- dc.contributor.author Lazcano, Rossana
- dc.contributor.author Mo, Chia-Kuei
- dc.contributor.author Davalos, Veronica
- dc.contributor.author Fortian, Arola
- dc.contributor.author Bernat, Adrià
- dc.contributor.author Romeo, Margarita
- dc.contributor.author Tokheim, Collin
- dc.contributor.author Barretina, Jordi
- dc.contributor.author Lazar, Alexander J.
- dc.contributor.author Ding, Li
- dc.contributor.author DUTRENEO Study Investigators
- dc.contributor.author Grande, Enrique
- dc.contributor.author Real, Francisco X.
- dc.contributor.author Esteller, Manel
- dc.contributor.author Bailey, Matthew H.
- dc.contributor.author Porta-Pardo, Eduard
- dc.date.accessioned 2025-02-20T13:00:57Z
- dc.date.available 2025-02-20T13:00:57Z
- dc.date.issued 2025
- dc.description.abstract Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we demonstrate interdependent relationships between hallmarks at the junctions of TME and cancer compartments and how they relate to sensitivity to different neoadjuvant treatments in 33 bladder cancer patients from the DUTRENEO trial. In conclusion, our findings may improve our understanding of tumor ecology and help identify new drug biomarkers.
- dc.description.sponsorship This research was funded by MCIN/AEI/10.13039/501100011033 and the ERDF through PID2021-125282OB-I00, Generalitat de Catalunya (2021 SGR 01494) and the Sarah Jennifer Knott Foundation. The authors would like to thank Abel Gonzalez-Perez, Nuria Lopez-Bigas, and Eliezer Van Allen for their valuable feedback and the kind and generous patients who donated the samples that made this study possible. This work has been done as part of the PhD Programme in "Biochemistry, molecular biology and biomedicine" from Universitat Autonoma de Barcelona.
- dc.format.mimetype application/pdf
- dc.identifier.citation Sibai M, Cervilla S, Grases D, Musulen E, Lazcano R, Mo CK, et al. The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity. Cell Rep. 2025 Jan 24;44(2):115229. DOI: 10.1016/j.celrep.2024.115229
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2024.115229
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/69655
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep. 2025 Jan 24;44(2):115229
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-125282OB-I00
- dc.rights © 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword CP: cancer
- dc.subject.keyword Cancer hallmarks
- dc.subject.keyword Drug sensitivity
- dc.subject.keyword Ecosystem
- dc.subject.keyword Intratumoral heterogeneity
- dc.subject.keyword Spatial transcriptomics
- dc.subject.keyword Tumor microenvironment
- dc.title The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion