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. LocasaleSherene 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

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)1589-1616
Number of pages28
Issue number7
StatePublished - 28 Mar 2024

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


Dive into the research topics of 'Embracing cancer complexity: Hallmarks of systemic disease'. Together they form a unique fingerprint.

Cite this