Hallmarks of cancer
There are several hundred types of cancer, arising from different tissues. Even tumours arising from the same tissue are increasingly recognised as comprising several different subtypes.
What characterises cancer is a shared constellation of abnormal cell behaviours, such as rapid cell division and invasion of surrounding tissue, which are linked to changes in DNA.
Cancer develops when the normal processes that control cell behaviour fail and a rogue cell becomes the progenitor of a group of cells that share its abnormal behaviours or capabilities. This generally results from accumulation of genetic damage in cells over time. The cancer cell is a critical part of a tumour but only one of several important types of cell that create the tumour microenvironment.
Although a bewildering variety of possible genetic changes can combine to cause cancer, the range of abnormal capabilities that cancer cells share is much narrower. These capabilities are known as the ‘hallmarks of cancer’.
The hallmarks of cancer:
- sustained proliferative signalling
- resisting cell death
- activating invasion and metastasis
- inducing angiogenesis
- evading growth suppressors
- enabling replicative immortality
- avoiding immune destruction
- deregulating cellular energetics
- enabling characteristic: genomic instability and mutation
- enabling characteristic: tumour-promoting inflammation
Rogue capabilities of cancer
The rogue capabilities of cancer cells, which can be so harmful to an organism, are not all unique to cancer. They are actually beneficial to some normal cells at certain times.
As an organism develops from a fertilised egg during embryonic and fetal life, its cells display a range of behaviours that are appropriate to each stage of development, but which tend to lie dormant at other times. These include capabilities that are typical of cancer cells, and include rapid cell division and invasion of surrounding tissues. Inappropriate and untimely activation of such capabilities in cells of an adult organism can mean those cells behave in the way that defines cancer. This can happen if the genetic changes that accumulate in cancer cells affect which genes are turned on or off.
One way of thinking about cancer, therefore, is that it is the inappropriate and abnormal resurrection of capabilities needed by cells during normal development after fertilisation.
Vulnerable to genetic damage
Almost all cells in an organism are vulnerable to damage to their DNA. For example, mutations can happen during cell division. Throughout life, an organism’s cells are constantly growing and dividing via a highly regulated process called the cell cycle. This allows tissues to grow and stay healthy. Before a cell divides, it must replicate its DNA (and therefore its genetic code), so that each of its two daughter cells has identical DNA to the parent cell. DNA replication is a complex process and is vulnerable to the introduction of errors in the DNA sequence.
DNA can be damaged at other times too. Cells are constantly exposed to factors that can damage DNA, either agents from the environment outside the body (exogenous), such as radiation or chemicals in cigarette smoke, or agents generated by processes that occur within the body (endogenous), such as free radicals or other by-products of metabolism. A substance or agent that is capable of causing cancer is known as a carcinogen, although not all carcinogens damage DNA directly.
Ageing allows increasing opportunity for cells to accumulate DNA damage. Ageing is also often accompanied by reduced capacity in many metabolic and physiological functions, including protection against DNA damage.
Use our glossary for explanations of the scientific terms
Cells can protect themselves …
Cells have evolved a range of mechanisms to prevent the accumulation of DNA damage, which protects them against acquiring the hallmarks of cancer. These mechanisms include:
- eliminating or detoxifying external agents that can cause DNA damage
- repairing DNA damage so it is not transmitted to daughter cells
- ensuring cells with damaged DNA do not survive
… but sometimes the protective mechanisms fail
The mechanisms that protect cells against accumulating DNA damage and the hallmarks of cancer are not perfect and may be compromised by several factors that can increase the risk of cancer, such as:
- inherited genetic defects
- high levels of exposure to external carcinogens
- endogenous factors that compromise DNA integrity
- reduced effectiveness of endogenous protective systems
Diet, nutrition and physical activity are essential aspects of human existence. Imbalanced and inappropriate levels of these factors can disturb normal homeostasis and reduce resilience to external challenges. This may manifest in many ways, for instance as susceptibility to infections, to cardiometabolic disease or to cancer.
Diet, nutrition and physical activity may influence cancer risk in a range of different ways. Some foods and drinks may be vectors for specific substances that act as carcinogens at particular sites. By contrast, obesity and sedentary ways of life may not act through single discrete pathways – instead, they may alter the systemic metabolic milieu of the body in ways that give rise to cellular microenvironments that are conducive to cancer development at a number of sites.
There is accumulating evidence on how diet, nutrition and physical activity can have an impact on the biological processes that underpin the development and progression of cancer – and influence whether cells acquire the phenotypic changes in cellular structure and function that are characterised as the hallmarks of cancer. For example:
- Inappropriate nutrition at the whole-body level is reflected in a disordered nutritional microenvironment at the cellular and molecular levels. This can create an environment that is conducive to the accumulation of DNA damage and therefore to cancer development.
- Obesity is associated with inflammatory mediators, and metabolic and endocrine abnormalities, that promote cell growth and exert anti-apoptotic effects, meaning cancer cells do not self-destruct even following severe DNA damage.
- Nutritional factors may influence mechanisms involved in DNA repair.
- Dietary compounds may influence pathways by which carcinogens are metabolised.
- Diet may influence epigenetic changes in cells.
- Drinking alcohol can increase production of metabolites that are genotoxic and carcinogenic.
- Reduced functional capacity, which occurs with inappropriate nutrition (and with ageing), reduces resilience to endogenous or external stresses.
- Physical activity has been shown to promote healthy immune and hormonal systems.
The growing body of evidence on such biological processes adds weight to evidence on effects of diet, nutrition and physical activity on cancer risk measured at the level of the whole body or indeed in whole populations in clinical or epidemiological studies.
This webpage is a summary. Download the full chapter for much more on the hallmarks of cancer and:
- body fatness
- dietary exposures
- physical activity
This webpage is a summary.
For much more, download the chapter PDF.