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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).
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.
Cancer is now understood to change its identity and behaviour without new mutations, to be shaped by bacteria inside and around it, and to be helped along by ageing cells. This explains why some tumours escape targeted drugs by changing cell type and why gut bacteria affect immunotherapy response.
This paper is why the tumour microenvironment is studied as intensely as the cancer cell itself. It underpins vaccination against HPV and hepatitis B as cancer prevention, aspirin and anti-inflammatory trials in bowel cancer, and the current work on macrophages and myeloid cells as immunotherapy targets.
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmark: inducing or accessing vasculature, Hallmarks of Cancer.
Shares Hallmark: enabling replicative immortality, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.