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The Hallmarks of Cancer is the most-cited framework in cancer biology: a short list of the capabilities every cancer must acquire, from unlimited growth to hiding from the immune system. The 2022 update lists eight hallmarks, two enabling characteristics, and four new dimensions.
Hanahan and Weinberg (2000, 2011) and Hanahan (2022). Core hallmarks: sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism, avoiding immune destruction. Enabling characteristics: genome instability and mutation, tumour-promoting inflammation. 2022 additions: unlocking phenotypic plasticity, non-mutational epigenetic reprogramming, polymorphic microbiomes, senescent cells. Each hallmark maps to drug classes; OnCo links every hallmark term to the pathways and technologies that address it.
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.
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.
Shares Enabling characteristic: tumour-promoting inflammation, Hallmark: inducing or accessing vasculature.
Shares Hallmark: enabling replicative immortality, Hallmark (2022): senescent cells, Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells.
Shares Cell, Hallmark: resisting cell death.
Shares Hallmark (2022): polymorphic microbiomes, Enabling characteristic: tumour-promoting inflammation, Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells.
Shares Hallmark: enabling replicative immortality, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmark (2022): unlocking phenotypic plasticity, Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Theories of cancer: how the ideas connect.
Shares Judah Folkman, Enabling characteristic: tumour-promoting inflammation, Hallmarks of cancer as a synthesis of the theories, Theories of cancer: how the ideas connect.
Shares Hallmark: reprogramming cellular metabolism, Theories of cancer: how the ideas connect.