Embracing cancer complexity: Hallmarks of systemic disease

Charles Swanton; Elsa Bernard; Chris Abbosh; Fabrice André; Johan Auwerx; Allan Balmain; Dafna Bar-Sagi; René Bernards; Susan Bullman; James DeGregori; Catherine Elliott; Ayelet Erez; Gerard Evan; Mark A Febbraio; Andrés Hidalgo; Mariam Jamal-Hanjani; Johanna A Joyce; Matthew Kaiser; Katja Lamia; Jason W Locasale; Sherene Loi; Ilaria Malanchi; Miriam Merad; Kathryn Musgrave; Ketan J Patel; Sergio Quezada; Jennifer A Wargo; Ashani Weeraratna; Eileen White; Frank Winkler; John N Wood; Karen H Vousden; Douglas Hanahan

doi:10.1016/j.cell.2024.02.009

Embracing cancer complexity: Hallmarks of systemic disease

Cell. 2024 Mar 28;187(7):1589-1616. doi: 10.1016/j.cell.2024.02.009.

Authors

Charles Swanton¹, Elsa Bernard², Chris Abbosh³, Fabrice André⁴, Johan Auwerx⁵, Allan Balmain⁶, Dafna Bar-Sagi⁷, René Bernards⁸, Susan Bullman⁹, James DeGregori¹⁰, Catherine Elliott¹¹, Ayelet Erez¹², Gerard Evan¹³, Mark A Febbraio¹⁴, Andrés Hidalgo¹⁵, Mariam Jamal-Hanjani¹⁶, Johanna A Joyce¹⁷, Matthew Kaiser¹¹, Katja Lamia¹⁸, Jason W Locasale¹⁹, Sherene Loi²⁰, Ilaria Malanchi²¹, Miriam Merad²², Kathryn Musgrave²³, Ketan J Patel²⁴, Sergio Quezada²⁵, Jennifer A Wargo²⁶, Ashani Weeraratna²⁷, Eileen White²⁸, Frank Winkler²⁹, John N Wood³⁰, Karen H Vousden³¹, Douglas Hanahan³²

Affiliations

¹ The Francis Crick Institute, London, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. Electronic address: charles.swanton@crick.ac.uk.
² The Francis Crick Institute, London, UK; INSERM U981, Gustave Roussy, Villejuif, France.
³ AstraZeneca, Cambridge, UK.
⁴ INSERM U981, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France; Paris Saclay University, Kremlin-Bicetre, France.
⁵ Laboratory of Integrative Systems Physiology, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
⁶ UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
⁷ NYU Langone Health, New York, NY, USA.
⁸ Division of Molecular Carcinogenesis, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
⁹ Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁰ Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹¹ Cancer Research UK, London, UK.
¹² Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
¹³ The Francis Crick Institute, London, UK; Kings College London, London, UK.
¹⁴ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
¹⁵ Department of Immunobiology, Yale University, New Haven, CT 06519, USA; Area of Cardiovascular Regeneration, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
¹⁶ Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
¹⁷ Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
¹⁸ Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA, USA.
¹⁹ Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA.
²⁰ Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Department of Medical Oncology, The University of Melbourne, Parkville, VIC, Australia.
²¹ The Francis Crick Institute, London, UK.
²² Department of immunology and immunotherapy, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²³ Translational and Clinical Research Institute, Newcastle University, Newcastle, UK; Department of Haematology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
²⁴ MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
²⁵ Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
²⁶ Department of Surgical Oncology, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁷ Sidney Kimmel Cancer Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²⁸ Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA; Ludwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton, NJ, USA.
²⁹ Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuro-oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
³⁰ Molecular Nociception Group, WIBR, University College London, London, UK.
³¹ The Francis Crick Institute, London, UK. Electronic address: karen.vousden@crick.ac.uk.
³² Lausanne Branch, Ludwig Institute for Cancer Research, Lausanne, Switzerland; Swiss institute for Experimental Cancer Research (ISREC), EPFL, Lausanne, Switzerland; Agora Translational Cancer Research Center, Lausanne, Switzerland. Electronic address: douglas.hanahan@epfl.ch.

PMID: 38552609
DOI: 10.1016/j.cell.2024.02.009

Abstract

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism and obesity, cancer cachexia, circadian rhythms, nervous system interactions, tumor-related thrombosis, and the microbiome. Model systems incorporating human genetic variation will be essential to decipher the mechanistic basis of these phenomena and unravel gene-environment interactions, providing a modern synthesis of molecular oncology that is primed to prevent cancers and improve patient quality of life and cancer outcomes.

Publication types

Review

MeSH terms

Carcinogenesis
Humans
Microbiota
Neoplasms* / genetics
Neoplasms* / pathology
Neoplasms* / therapy
Obesity / complications
Quality of Life