The Hallmarks of Cancer: six capabilities every tumour must acquire
Hanahan and Weinberg distilled decades of cancer biology into six acquired capabilities shared by all cancers, giving the field a common organising framework that has been cited more than any other cancer paper.
Written for the millennium issue of Cell, this review proposed that the vast catalogue of cancer genotypes is a manifestation of six essential alterations in cell physiology: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. Genome instability was presented as the enabling characteristic that lets cells acquire these traits.
The authors argued that tumours are not simply masses of proliferating cells but tissues composed of many cell types, anticipating the later emphasis on the microenvironment. They also predicted that cancer research would become a logical science with mechanism-based therapies targeting each hallmark.
The 2011 update added two hallmarks (reprogramming energy metabolism, evading immune destruction) and two enabling characteristics (genome instability, tumour-promoting inflammation).
- Six hallmarks: sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis
- Genome instability proposed as the enabling characteristic underlying acquisition of the hallmarks
- Tumours framed as complex tissues in which stromal and immune cells are active participants
- The paper became the most-cited article in Cell and one of the most-cited in biomedicine
The hallmarks are the mental map most oncologists and researchers use to think about what cancer is and where drugs act. A newcomer can understand nearly every therapy as an attack on one hallmark: kinase inhibitors on proliferative signalling, checkpoint blockade on immune evasion, anti-VEGF drugs on angiogenesis.
- A conceptual review rather than new data; critics argue it over-generalises across very different diseases
- Some hallmarks (angiogenesis) turned out to be less universally targetable than hoped
- Did not anticipate the centrality of the immune system or of epigenetic and microbial factors, later added
- Provides no quantitative framework for prioritising targets
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not linked directly; found by shared links- TermHallmark (2022): senescent cells
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer.
- PersonJudah Folkman
Shares Hallmark: inducing or accessing vasculature, Hallmarks of Cancer.
- TermHallmark (2022): non-mutational epigenetic reprogramming
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer.
- TermHallmark (2022): polymorphic microbiomes
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer.
- TermHallmark (2022): unlocking phenotypic plasticity
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer.
- PathwayCellular senescence
Shares Hallmark: enabling replicative immortality, Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells.
- TermOncogene
Shares Hallmark: sustaining proliferative signalling, Oncogene addiction.
- IdeaA real-world sequencing analysis within a year of every new approval
Shares Too many combinations to test, Knowledge reaches practice too slowly.