Faculty, Staff and Student Publications

Publication Date

2-25-2025

Journal

Cell Reports

DOI

10.1016/j.celrep.2024.115229

PMID

39864059

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.

Keywords

Humans, Tumor Microenvironment, Neoplasms, Urinary Bladder Neoplasms, Transcriptome, Antineoplastic Agents, Drug Resistance, Neoplasm

Published Open-Access

yes

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