1. Mutations in Genes Controlling Cell Growth and Division:
* Proto-oncogenes: These genes normally promote cell growth and division. Mutations can turn them into oncogenes, which constantly signal for cell growth, regardless of the body's need.
* Tumor Suppressor Genes: These genes normally act as "brakes" on cell growth, stopping or repairing damaged cells. Mutations can disable these genes, allowing damaged cells to proliferate unchecked.
2. External Factors Contributing to Mutations:
* Carcinogens: These are substances that damage DNA, increasing the likelihood of mutations in proto-oncogenes and tumor suppressor genes. Examples include tobacco smoke, UV radiation, certain chemicals, and viruses.
* Inflammation: Chronic inflammation can lead to DNA damage and create an environment conducive to tumor growth.
3. Deregulation of the Cell Cycle:
* Checkpoints: The cell cycle has checkpoints that ensure proper DNA replication and repair before a cell divides. Mutations can disrupt these checkpoints, allowing cells with damaged DNA to replicate.
* Growth Factors: Signals from growth factors are crucial for cell division. Mutations can lead to cells becoming hypersensitive to these signals, promoting uncontrolled growth.
4. Cellular Immortality:
* Telomerase: This enzyme is responsible for maintaining the ends of chromosomes, preventing them from shortening with each cell division. Normally, telomerase activity decreases with age, limiting cell division. Cancer cells often reactivate telomerase, allowing them to divide indefinitely.
5. Angiogenesis:
* Tumor Growth Requires Blood Supply: Tumors need a constant supply of oxygen and nutrients. They induce the formation of new blood vessels (angiogenesis) to sustain their growth.
Important Points:
* Tumor Growth is a Multi-Step Process: Multiple genetic and environmental factors typically need to occur before a tumor develops.
* Not All Mutations Lead to Cancer: The body has mechanisms to repair DNA damage and eliminate abnormal cells.
* Tumors are Heterogeneous: Cancer cells within a tumor can have different genetic alterations, making them more resistant to therapies.
In essence, tumor formation is a consequence of disruptions in the delicate balance of cell growth, division, and death, leading to a population of cells that escape normal controls and proliferate uncontrollably.
