In two landmark scientific papers, Douglas Hanahan of the University of California, San Francisco and Robert Weinberg of the Massachusetts Institute of Technology described the Hallmarks of Cancer this way:
Self-Sufficient Cell Division
Cells are organized into tissues and tissues are organized into organs with specific functions, such as the heart, lungs and skin. The cells of each organ must work and communicate as a team to function properly. When growth is necessary, cells collectively send signals to other cells to divide. Cancer cells, on the other hand, do not behave as team members. They control their own proliferation by producing growth signals themselves or by having overactive signal receptors.
Insensitivity to signals to stop cell division
Just as there are signals that stimulate cell proliferation, there are signals that put the brakes on cell growth and proliferation. Cancer cells are able to interrupt or ignore these inhibitory messages. Usually this is a result of mutations or alterations to genes known as tumor suppressor genes, which normally control a cell’s response to external and internal cues to exit the cell division cycle.
Resisting cell death (apoptosis or cell suicide)
When cells become old or damaged they are programmed to die in a process called apoptosis. This is the body’s way of limiting growth and discarding cells with damaged DNA in order to prevent propagation of DNA errors. Cancer cells are dangerous because they avoid the normal cell death cycle and continue to accumulate in the body. Apoptosis signals can be disrupted when tumor suppressor genes suffer mutations or other damage.
Limitless reproductive potential
The accumulation of the billions of cells it takes to form a tumor requires uncontrolled cell division, avoidance of apoptosis and the ability to replicate an unlimited number of times. In normal cell division, a small portion of the end of each chromosome, in a region called the telomere, is lost every time DNA is copied. Eventually the loss of telomere reaches a critical point and the cell can no longer divide and replicate. In this way, healthy cells self-limit their replication, but activation of an enzyme called telomerase can maintain telomeres and allow the cell to continue to replicate indefinitely. More than 90 percent of “immortalized” cancer cells have activated telomerase, while most normal cells do not.
Creating their own blood supply (angiogenesis)
In order for a tumor to grow it needs a greater and greater blood supply to provide oxygen and nutrients to the increasing number of cells. A tumor is able to stimulate formation of new blood vessels, a process known as angiogenesis, to supply it with adequate nutrients and promote its growth.
Ability to invade other organs (metastasis)
Cancer cells, unlike normal cells, can metastasize – break through tissue barriers and spread from one organ to another. Sometimes they do this by entering the newly formed blood vessels created by the tumor.
Ability to survive with little oxygen (the Warburg effect)
Even with an increased blood supply, cells in the interior of a tumor may be oxygen- and nutrient-deprived. This would be detrimental to normal cells, which use oxygen to convert glucose to energy through the process of aerobic metabolism. Cancer cells have the ability to switch from aerobic to anaerobic (oxygen-free) glucose metabolism (glycolysis) to allow oxygen-deprived cells to continue to produce energy and survive.
Evading the immune system
When functioning properly, the body’s immune system detects and destroys foreign and abnormal cells. Although the process is not fully understood, there is evidence that cancer cells are able to evade destruction by the body’s immune defenses to some degree, allowing them to proliferate and invade other tissues.
These eight hallmark characteristics that distinguish cancer cells from normal ones are made possible by two final characteristics that enable the alterations necessary for a cell to become cancerous:
Genomic instability
Genes are segments of DNA that provide the instructions for all cellular activity. The accumulation of changes to specific genes that promote cell proliferation (e.g., activating oncogenes) or disrupt control mechanisms (e.g., tumor suppressor genes) can result in normal cells acquiring hallmark characteristics and transforming into cancer cells.
Inflammation
Chronic inflammation can result in conditions that promote proliferation, cell survival and angiogenesis. Inflammation can also enhance production of free radicals that can damage DNA.
