8 Hallmarks of Cancer Pathophysiology
See details of these hallmarks in separate tutorials:
Cancer Pathophysiology 1
Cancer Pathophysiology 2
Cancer cells are self-sufficient
They promote their own self replication in the absence of the external signals non-cancer cells rely on.
To illustrate this in the nucleus of our diagram, we sketch the phases of the
cell cycle; we show that cancer cells move through the stages, especially G1, at an accelerated rate.
Cancer cells ignore growth suppressors
This means there's no time for DNA repair, in part because cancer cells do not pause between the G1 and S phases.
Cancer cells evade apoptosis
Thus, cells survive despite DNA damage.
Cancer cells are immortal
They evade the
mitotic crisis that results in the death of non-cancer cells.
Thus, cancer cells continue replication and perpetuate the DNA damage.
For example, the telomeres of cancer cells do not shorten over time.
Telomeres are protective end-caps, that, in normal somatic cells, shorten with each replication. Eventually, they are too short to protect the chromosomal DNA, and the cell dies.
However, telomeres are maintained in cancer cells by an enzyme called telomerase. Thus, the telomeres do not shorten and cell death is avoided.
Cancer cells exhibit altered metabolism
Also called the Warburg effect, this enables them to meet their unique metabolic needs.
Cancer cells use aerobic
glycolysis to fuel biosynthesis of new organelles; thus, cancer cells are characterized by increased glucose and glutamine consumption.
To set up the diagram, we show the extracellular matrix and a blood vessel. Then, we draw a cancer cell, and show that it undergoes clonal expansion and diversification to form a primary tumor; this
development was enabled by the physiological changes we indicated, above.
Cancer cells trigger angiogenesis
Formation of new blood vessels from existing vasculature enables the tumor to meet its nutritional needs.
The "angiogenic switch" is triggered by tumors greater than 2 cm; below this threshold, simple diffusion suffices.
Cancer cells invade and metastasize
This enables them to cross anatomical boundaries. In contrast, the growth of benign tumors is limited by anatomical boundaries.
Cancer cells break free from the primary tumor.
They invade the extracellular matrix and migrates to a nearby vessel.
Then, in a process called
intravasation, the cancer cells enter circulation. Be aware that cancer cells can enter blood and/or lymphatic vessels, and that some cancers are more prone to a specific vessel type.
Cancer cells travel within the circulation, where they can form an embolus with T lymphocytes and platelets. This aggregation may protect the cancer cells from destruction.
Cancer cells can break free from the embolus and exit the vessel, a process called
extravasation.
In their new environment, the cancer cells can proliferate to form a metastatic tumor; show that this tumor can also develop its own blood supply.
Invasion and metastasis are major causes of morbidity and death from cancer.
Cancer cells evade the immune system
Ensures their own survival.
They can downregulate expression of MHC proteins and presentation of antigens on their own cell surfaces. Thus, they "hide" from the immune system.
They can also suppress immune cell responses and release immunosuppressive cytokines, which dampens the ability of the immune system to defend the host.
