The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity
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...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015808 |
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| author | Mustafa Sibai Sergi Cervilla Daniela Grases Eva Musulen Rossana Lazcano Chia-Kuei Mo Veronica Davalos Arola Fortian Adrià Bernat Margarita Romeo Collin Tokheim Jordi Barretina Alexander J. Lazar Li Ding Enrique Grande Francisco X. Real Manel Esteller Matthew H. Bailey Eduard Porta-Pardo Enrique Grande Teresa Alonso-Gordoa Mario Álvarez-Maestro Elena Andrada Ainara Azueta Raquel Benítez Javier Burgos Daniel Castellano M. Angel Climent Mario Domínguez Ignacio Durán Albert Font Isabel Galante Patricia Galván Juan F. García Xavier García del Muro Félix Guerrero-Ramos Núria Malats Miriam Marqués Pablo Maroto Jaime Martínez de Villarreal Ane Moreno-Oya Jesús M. Paramio Alvaro Pinto Aleix Prat Javier Puente Oscar Reig Francisco X. Real |
| author_facet | Mustafa Sibai Sergi Cervilla Daniela Grases Eva Musulen Rossana Lazcano Chia-Kuei Mo Veronica Davalos Arola Fortian Adrià Bernat Margarita Romeo Collin Tokheim Jordi Barretina Alexander J. Lazar Li Ding Enrique Grande Francisco X. Real Manel Esteller Matthew H. Bailey Eduard Porta-Pardo Enrique Grande Teresa Alonso-Gordoa Mario Álvarez-Maestro Elena Andrada Ainara Azueta Raquel Benítez Javier Burgos Daniel Castellano M. Angel Climent Mario Domínguez Ignacio Durán Albert Font Isabel Galante Patricia Galván Juan F. García Xavier García del Muro Félix Guerrero-Ramos Núria Malats Miriam Marqués Pablo Maroto Jaime Martínez de Villarreal Ane Moreno-Oya Jesús M. Paramio Alvaro Pinto Aleix Prat Javier Puente Oscar Reig Francisco X. Real |
| author_sort | Mustafa Sibai |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-2c6bd52806f54063a4a4eba14517806d |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-2c6bd52806f54063a4a4eba14517806d2025-01-26T05:03:48ZengElsevierCell Reports2211-12472025-02-01442115229The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivityMustafa Sibai0Sergi Cervilla1Daniela Grases2Eva Musulen3Rossana Lazcano4Chia-Kuei Mo5Veronica Davalos6Arola Fortian7Adrià Bernat8Margarita Romeo9Collin Tokheim10Jordi Barretina11Alexander J. Lazar12Li Ding13Enrique Grande14Francisco X. Real15Manel Esteller16Matthew H. Bailey17Eduard Porta-Pardo18Enrique GrandeTeresa Alonso-GordoaMario Álvarez-MaestroElena AndradaAinara AzuetaRaquel Benítez Javier BurgosDaniel CastellanoM. Angel ClimentMario DomínguezIgnacio Durán Albert FontIsabel GalantePatricia GalvánJuan F. GarcíaXavier García del MuroFélix Guerrero-RamosNúria MalatsMiriam MarquésPablo MarotoJaime Martínez de VillarrealAne Moreno-OyaJesús M. ParamioAlvaro PintoAleix PratJavier PuenteOscar ReigFrancisco X. RealJosep Carreras Leukaemia Research Institute (IJC), Badalona, Spain; Barcelona Supercomputing Center (BSC), Barcelona, SpainJosep Carreras Leukaemia Research Institute (IJC), Badalona, SpainJosep Carreras Leukaemia Research Institute (IJC), Badalona, SpainJosep Carreras Leukaemia Research Institute (IJC), Badalona, Spain; Department of Pathology, Hospital Universitari General de Catalunya Grupo-QuirónSalud, Sant Cugat del Vallès, SpainThe University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USAJosep Carreras Leukaemia Research Institute (IJC), Badalona, SpainInstitut de Recerca Germans Trias i Pujol (IGTP), Badalona, SpainInstitut de Recerca Germans Trias i Pujol (IGTP), Badalona, SpainInstitut de Recerca Germans Trias i Pujol (IGTP), Badalona, SpainDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA, USAInstitut de Recerca Germans Trias i Pujol (IGTP), Badalona, SpainThe University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USAMedical Oncology Department. MD Anderson Cancer Center Madrid, Madrid, SpainCentro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; Centro de Investigación Biomedica en Red Cancer (CIBERONC), Madrid, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, SpainJosep Carreras Leukaemia Research Institute (IJC), Badalona, Spain; Centro de Investigación Biomedica en Red Cancer (CIBERONC), Madrid, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, SpainDepartment of Biology and Simmons Center for Cancer Research, Brigham Young University, Provo, UT, USAJosep Carreras Leukaemia Research Institute (IJC), Badalona, Spain; Barcelona Supercomputing Center (BSC), Barcelona, Spain; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724015808CP: cancer |
| spellingShingle | Mustafa Sibai Sergi Cervilla Daniela Grases Eva Musulen Rossana Lazcano Chia-Kuei Mo Veronica Davalos Arola Fortian Adrià Bernat Margarita Romeo Collin Tokheim Jordi Barretina Alexander J. Lazar Li Ding Enrique Grande Francisco X. Real Manel Esteller Matthew H. Bailey Eduard Porta-Pardo Enrique Grande Teresa Alonso-Gordoa Mario Álvarez-Maestro Elena Andrada Ainara Azueta Raquel Benítez Javier Burgos Daniel Castellano M. Angel Climent Mario Domínguez Ignacio Durán Albert Font Isabel Galante Patricia Galván Juan F. García Xavier García del Muro Félix Guerrero-Ramos Núria Malats Miriam Marqués Pablo Maroto Jaime Martínez de Villarreal Ane Moreno-Oya Jesús M. Paramio Alvaro Pinto Aleix Prat Javier Puente Oscar Reig Francisco X. Real The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity Cell Reports CP: cancer |
| title | The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity |
| title_full | The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity |
| title_fullStr | The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity |
| title_full_unstemmed | The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity |
| title_short | The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity |
| title_sort | spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity |
| topic | CP: cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015808 |
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