In addition to the six acquired capabilities-Hallmarks of Cancer-proposed in 2000 (1), the two provisional “emerging hallmarks” introduced in 2011 (2)-cellular energetics (now described more broadly as “reprogramming cellular metabolism”) and “avoiding immune destruction”-have been sufficiently validated to be considered part of the core set.
Left, the Hallmarks of Cancer currently embody eight hallmark capabilities and two enabling characteristics. In essence: the Hallmarks of Cancer, circa 2022. While appreciating that such specialized mechanisms can be instrumental, we limited the hallmarks designation to parameters having broad engagement across the spectrum of human cancers. Certainly, the diversity of malignant pathogenesis spanning multiple tumor types and an increasing plethora of subtypes includes various aberrations (and hence acquired capabilities and characteristics) that are the result of tissue-specific barriers necessarily circumvented during particular tumorigenesis pathways. This formulation was influenced by the recognition that human cancers develop as products of multistep processes, and that the acquisition of these functional capabilities might be mapped in some fashion to the distinguishable steps of tumor pathogenesis. Initially we envisaged the complementary involvement of six distinct hallmark capabilities and later expanded this number to eight. The intent was to provide a conceptual scaffold that would make it possible to rationalize the complex phenotypes of diverse human tumor types and variants in terms of a common set of underlying cellular parameters.
In these articles ( 1, 2), Bob Weinberg and I enumerated what we imagined were shared commonalities that unite all types of cancer cells at the level of cellular phenotype. The Hallmarks of Cancer were proposed as a set of functional capabilities acquired by human cells as they make their way from normalcy to neoplastic growth states, more specifically capabilities that are crucial for their ability to form malignant tumors.
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