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The third hallmarks paper proposed two new hallmarks (unlocking phenotypic plasticity, senescent cells) and two new enabling characteristics (non-mutational epigenetic reprogramming, polymorphic microbiomes), bringing the framework to fourteen elements.
Twenty-two years after the original, Douglas Hanahan reviewed developments that the 2000 and 2011 frameworks did not accommodate. He proposed unlocking phenotypic plasticity (dedifferentiation, blocked differentiation and transdifferentiation, as in neuroendocrine transformation of prostate and lung cancers) as a hallmark, and senescent cells as a distinct cell type contributing to tumour progression.
He added non-mutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics: mechanisms by which cells acquire hallmark capabilities without new mutations, and ways in which microbial communities in gut and tumour modulate cancer risk, progression and therapy response.
The paper reflects how much lineage plasticity, epigenetics and the microbiome now feature in drug development, including for resistance to targeted therapy and immunotherapy.
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.
Shares The Hallmarks of Cancer: six capabilities every tumour must acquire, Hallmarks of Cancer, Cellular senescence.
Shares The Hallmarks of Cancer: six capabilities every tumour must acquire, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares The Hallmarks of Cancer: six capabilities every tumour must acquire, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares The Hallmarks of Cancer: six capabilities every tumour must acquire, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmarks of Cancer, Microbiome-tumour interactions, Hallmarks of cancer as a synthesis of the theories.
Shares The Hallmarks of Cancer: six capabilities every tumour must acquire, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares The Hallmarks of Cancer: six capabilities every tumour must acquire, Hallmarks of Cancer, Hallmarks of cancer as a synthesis of the theories.
Shares Hallmark (2022): non-mutational epigenetic reprogramming, Cellular senescence, Cancer stem cells & phenotypic plasticity, Epigenetic reprogramming.