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Cancer Pathophysiology Overview

Notes

Cancer Pathophysiology Overview

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8 Hallmarks of Cancer Pathophysiology

See details of these hallmarks in separate tutorials:
Cancer Pathophysiology 1

Cancer Pathophysiology 2

Intracellular Effects

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.

Extracellular Effects

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.

Full-Length Text

  • Here we will learn 8 hallmarks of cancer pathophysiology.
  • To begin, indicate that these hallmarks include both intra- and extracellular effects.

We'll begin with the intracellular effects.

  • First, draw a cell, and indicate the cytoplasm, nucleus, and a representative mitochondrion.
  • Then, write that cancer cells are self-sufficient, which means that they promote their own self replication in the absence of the external signals non-cancer cells rely on.
  • To illustrate this, move to the nucleus in our diagram, and sketch the phases of the cell cycle; show that cancer cells move through the stages, especially G1, at an accelerated rate.
  • Then, write that cancer cells ignore growth suppressors;
  • Indicate that this means there's no time for DNA repair, in part because cancer cells do not pause between the G1 and S phases.
  • Next, indicate that cancer cells evade apoptosis; thus, cells survive despite DNA damage.
  • Cancer cells are also immortal; that is, they evade the mitotic crisis that results in the death of non-cancer cells.
    • Thus, cancer cells continue replication and perpetuate the DNA damage.
  • To illustrate an example of this, draw a chromosome, and highlight its telomeres.
    • 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, indicate that the telomeres are maintained in cancer cells by an enzyme called telomerase.
    • Thus, the telomeres do not shorten and cell death is avoided.
  • Next, write that cancer cells exhibit altered metabolism, sometimes called the Warburg effect, which enables them to meet their unique metabolic needs.
  • In the mitochondrion of our diagram, indicate that cancer cells use aerobic glycolysis to fuel biosynthesis of new organelles; thus, cancer cells are characterized by increased glucose and glutamine consumption.
  • Next, let's consider three ways that cancer cells interact with and influence their extracellular environments.
  • First, show the extracellular matrix and a blood vessel.
  • Then, 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.
  • Now, write that cancer cells trigger angiogenesis, which is the formation of new blood vessels from existing vasculature.
  • Write that this enables the tumor to meet its nutritional needs. Interestingly, the "angiogenic switch" is triggered by tumors greater than 2 cm; below this threshold, simple diffusion suffices.
  • Next, write that cancer cells invade and metastasis, which enables them to cross anatomical boundaries.
    • In contrast, the growth of benign tumors is limited by anatomical boundaries.
  • To illustrate this, show a cell breaking free from the primary tumor.
  • Show that it invades the extracellular matrix and migrates to a nearby vessel.
  • Then, in a process called intravasation, the cancer cell enters 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.
  • Next, show that the 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.
  • Now, show that 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.
    • Be aware that invasion and metastasis are major causes of morbidity and death from cancer.
  • Finally, indicate that cancer cells evade the immune system, which ensures their own survival.

In our diagram, indicate a few examples of how cancer cells achieve this:

  • First, 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.

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