How do cancer cells overcome immune and check responses of the body against cancer to flourish and become full blown cancer. Cancer cells adopt various mechanisms to bypass these safety mechanisms of the human body. These mechanisms adopted by the cancer cells are known as hallmarks of cancer. Cancer cells are formed by a sequential process of genetic mutations. For normal cells to start the chain of malignant cell divisions these 10 hallmarks are necessary as described below.
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1. Genetic Mutations:
Human genetic material is unstable and human genome can gather expansions resulting in unwanted mutations, which can lead to formation of malignant cells. Normally there are enough check mechanisms that force these cells, with unwanted genetic material, into dormancy or apoptosis. When these surveillance mechanisms become compromised then relentless growth of cancer cells starts.
2. Evading Cell Demise:
Cancer cells are extremely resistant to cell death. Healthy cells die through three major mechanisms of cell death. These three mechanisms include apoptosis, autophagy and necrosis
Apoptosis is programmed cell death, which ensues when a cell has completed its natural life span resulting in weak links in DNA. Young cells with abnormal DNA are also phased out with this mechanism.
Apoptosis is significantly diminished in cancer cells populations especially those, which are high grade and are resistant to treatment.
Many factors regulate apoptosis but the most important one is tumor suppressor gene TP 53. This gene can initiate apoptosis in cells with significantly altered DNA. Cellular injury activates TP53 gene to initiate apoptosis. This activation mostly results from cellular injury due to DNA damage caused by chemotherapy, damage from oxidation and radiation damage by ultraviolet rays.
Autophagy is a destructive process that causes lysosomal enzyme mediated destruction of the contents of the cell. This is a normal physiological process that is going on inside the cells at a smaller scale. This process can be initiated with the help of cytodestructive stimuli such as radiation and chemotherapy. These processes have been shown to suppress cancer cells if severe stress has been applied onto them, however this suppression is reversible so that when the stimulus for autophagy is withdrawn resurgence of these suppressed cancer cells can occur. While if the cytodestructive stimuli cannot put severe stress onto the cancer cells then this process of autophagy kills only normal cells and becomes protective for the cancer cells.
Death of young cells i.e. before completion of their natural life span is called necrosis. Cells after necrosis release certain mediators into the surrounding environment that encourage recruitment of inflammatory cells, which in turn causes inflammation, cellular proliferation and new blood vessel formation. This property of cellular proliferation secondary to necrosis makes it a procancer and not an anticancer factor.
3. Persistent Signals for Cellular Proliferation:
Proliferation and growth of cancer cells is unstoppable because of binding of growth factors to cell surface-bound receptors that in turn leads to activation of an intracellular signaling cascade, which is dependent on tyrosine kinase. This activated signaling process leads to altered genetic expression and enhanced cellular proliferation and growth. This relentless growth of cancer cells is supported by excessive production of growth factor ligands or excessive production of abnormal receptors that do not require ligands for activation hence providing endless supply of cell-proliferating signals.
4. Overcoming Growth Suppression:
Normal cell populations observe growth restriction and suppression due to adjoining cells in thick cell populations. While shameless cancer cells have no inhibition of adjoining cells whatsoever when it comes to endless growth.
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