The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity

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 t...

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Bibliographic Details
Authors: Sibai, Mustafa, Cervilla García, Sergi, Grases, Daniela, Musulen, Eva, Lazcano, Rossana, Mo, Chia-Kuei, Davalos, Veronica, Fortian, Arola, Bernat, Adrià, Romeo, Margarita, Tokheim, Collin, Barretina, Jordi, Lazar, Alexander J., Ding, Li, DUTRENEO Study Investigators, Grande, Enrique, Real, Francisco X., Esteller, Manel, Bailey, Matthew H., Porta-Pardo, Eduard
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/69655
Online Access:http://hdl.handle.net/10230/69655
http://dx.doi.org/10.1016/j.celrep.2024.115229
Access Level:Open access
Keyword:CP: cancer
Cancer hallmarks
Drug sensitivity
Ecosystem
Intratumoral heterogeneity
Spatial transcriptomics
Tumor microenvironment
Description
Summary: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.

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