All tumor cells begin as normal cells; however, these cells have found a way to acquire new biological abilities now termed the hallmarks of cancer. There are 10 hallmarks of cancer:
- Sustained proliferative signaling- Normal cells will only replicate when the appropriate signals are given indicating that there is sufficient space, nutrients, and new cells are needed. Cancer cells make more cells without the proper signal being given.
- Evading growth suppressors- Normal cells will stop dividing when given signals that conditions are no longer favorable for division. Cancer cells ignore the signal to stop dividing.
- Resisting cell death- Normal cells activate apoptosis or cell death when something is wrong with the cell or if there are errors that cannot be repaired in the DNA during replication. Cancer cells ignore these signals; therefore they do not die when they should.
- Enabling replicative immortality- Normal cells stop dividing after a certain number of divisions determined by the length of their telomeres. Cancer cells do not stop dividing at that point; they may even extend their own 'clock' by activating an enzyme to lengthen their telomeres. This makes cancer cells immortal.
- Inducing angiogenesis- Cells need oxygen to live. Cancer cells ensure their newly made cells survive by creating new blood vessels to feed oxygen and nutrients to the cancer cells.
- Avoiding Immune Destruction- Cancer cells can gain the ability to hide from immune cell destruction by upregulating proteins such as programmed death ligand 1 (PD-L1) that deactivate T-cells.
- Activating invasion and metastasis- Normal cells respect the natural barriers of their environment. Cancer cells invade membranes and even break off of the tumor and travel throughout the body and create new tumors.
- Deregulating cellular energetics- Cancer cells divide rapidly and therefore need more energy than normal cells. Normal cells use oxygen to make energy in a process called oxidative phosphorylation. Often cancer cells are in anaerobic conditions and therefore need to be able to make energy without oxygen. Cancer cells circumvent this issue by using anaerobic glycolysis to make energy or ATP.
- Tumor-promoting inflammation- Immune cells are found within tumors. Originally it was thought that these immune cells were there to fight off the cancer cells. Research has shown that the cancer cells have intercepted these tumor infiltrating immune cells and use them to help them promote tumor progression.
- Genome instability and mutation- Normal cells stop during replication to inspect the newly made DNA and ensure that the DNA is error-free. Cancer cells bypass these checkpoints and therefore introduce more errors per replication cycle. Cancer cells are also going through more cycles of replication than a normal cell does. Additionally, if errors are introduced into DNA repair genes that render the protein useless, the error rate in the cancer genome will go up even more rapidly. This leads to cancer cells having a highly unstable and mutated genome.
Because the hallmarks of cancer differentiate cancer cells from normal cells, these pathways become targets for pharmaceutical agents to try and selectively kill cancer cells without affecting normal cells.
