Hallmarks of Cancer

Cancer is a complex disease involving both genetic and epigenetic alterations that affect a large number of genes, proteins and signalling networks during tumor progression. Normal cells require certain characteristics, i.e. hallmarks, in order to become malignant. Hanahan and Weinberg (2000; 2011), have proposed a framework comprising eight hallmarks and two enabling characteristics, as an organizing principle to simplify the diversity of the biological processes leading to cancer.

The Hallmarks of Cancer

Sustaining proliferative signaling

Proliferative signalling- cell cycle

The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. [GO:0007049]

Growth signals

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a growth factor stimulus. [GO:0071363]

Growth signals – downstream signalling

The temporal and mechanistic order of cellular and molecular events. For example, in signal transduction, the second messenger acts downstream to activation of cell membrane receptors.

Proliferative signalling - receptors

The growth factor receptors (such as EGFR) are cell membrane receptors that after being activated by e.g. a hormone or a growth factor, initiate the signal transduction pathway.


Evading growth suppressors

Deregulating cell cycle

Deregulating the progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. [GO:0007049]

Evading contact inhibition

A growth control mechanism by which cells stop growing or dividing depending on the conditions e.g. increased cell density. [GO:0060242]


Avoiding immune destruction

Immune response

Any immune system process that recognises and defends an organism with a calibrated response against any potential internal or foreign threat. [GO:0006955]

Immunosuppression

Any process that stops, prevents, or reduces the frequency, rate or extent of the immune response, the immunological reaction of an organism to an immunogenic stimulus. [GO:0050777]


Enabling replicative immortality

Immortalization

A phenomenon under which the modifications in a cell enable it to reproduce indefinitely. [GO:0020021]

Senescence

A biological aging process that involves gradual dysfunctional changes by which a cell become less capable of maintaining physiological functions e.g. normal cells lose the ability to divide through irreversible cell cycle arrest. [GO:0090398]


Tumor-promoting inflammation

Inflammation

The immediate defensive reaction of body tissues to infection or injury caused by chemical or physical agents. [GO:0006954]

Oxidative stress

A condition characterized by an imbalance between the systemic manifestation of reactive oxygen species and the ability of a biological system to readily detoxify the reactive intermediates or repair the resulting damage to cellular environment.[MP:0003674]


Activating Invasion and metastasis

Invasion

The infiltration or penetration of neoplasms to actively destroy the surrounding tissues of its primary site. [GO:0044409]

Metastasis

The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. [MeSH:D009362]


Inducing angiogenesis

Deregulating angiogenesis

A physiological process of blood vessel formation through which new vessels emerge from the proliferation of pre-existing blood vessels. [GO:0001525]

Angiogenic factors

Multiple factors including soluble growth and differentiative factors, extracellular matrix components, membrane-bound receptors, and intracellular signaling molecules which contribute to angiogenesis. For example: VEGF, FGF etc.


Genomic instability and mutation

DNA damage

Drug-, chemical-, radiation-induced, or spontaneous injuries to the chemical structure of DNA e.g. break in the strand of DNA. [ncithesaurus:C16507]

DNA adducts

DNA adducts are formed after covalent bonding between a molecule e.g. chemical and the DNA macromolecule that may interfere with DNA replication and repair. [ncithesaurus:C25825]

DNA strand breaks

A DNA strand break involves one or more disruptions of the covalent linkages among phosphor-deoxyribose moieties within the sugar-phosphate backbone in one or in both strands of a DNA molecule. [ncithesaurus:C25830]

DNA repair

A collection of cellular processes that maintain the original DNA sequence by identifying and correcting the damage to the DNA molecule. For example; base excision repair, double-strand break repair, and mismatch repair etc. [GO:0006281]

Mutation

Any permanent change in the DNA sequence of a cell or the genome of an organism, which can result from radiation, viral infection, transposition, mutagenic chemicals and/or from errors during DNA replication or meiosis. [ncithesaurus:C45576]


Resisting cell death

Apoptosis

A highly regulated and controlled cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. [GO:0006915]

Autophagy

The natural process in which cells digest or disassemble the unnecessary or dysfunctional cellular components; thereby allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation. [GO:0006914]

Necrosis

A premature cell death that involves unregulated digestion of cell component as a result of infection, toxins or trauma. It is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus […] and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. [GO:0070265]


Deregulating cellular energetics

Glycolysis/ Warburg effect

The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. [GO:0006096]