Part 1: What is cancer?
This semester, I have been taking a Cancer Biology course. In this article, I’d like to share some of the things I have learned, review why cancer has been so hard to cure, and discuss the outlook for the future of cancer research.
Our knowledge of cancer and how it develops has increased tremendously since President Nixon launched the “War on Cancer” in 1971. Even though we understand many of the mechanisms of cancer progression, we’re still losing the war. The main treatments today, such as radiation and chemotherapy, are the same treatments used in the 1970’s. Incidences of most types cancers have remained steady and rates of death have only slightly decreased.
Cancer is the result of uncontrolled tissue growth. In order for a cell to divide it must pass through certain “checkpoints” to ensure that the division is occurring at an appropriate time and place. The act of a cell passing through these checkpoints and ultimately dividing is known as the “cell cycle.”
Several key genes regulate the passage of the cell through the cell cycle. Some are positive regulators, called “proto-oncogenes,” pushing the cell forward through the cell cycle. Others are negative regulators, called “tumor suppressors,” holding the cell back and slowing cell growth. These genes work in concert to maintain balanced and appropriate cell growth.
When a few of these genes become deregulated, through mechanisms such as gene mutations, the cell can continuously speed through the cell cycle resulting in an overabundance of cells and tumor formation. In simple terms, cancer is the overgrowth of our own cells.
So what causes these DNA mutations that lead to cancer?
Before a cell divides, it makes an extra copy of its DNA. This way, when the cell divides each of the two resulting cells will have a full copy of the DNA. Ultimately, the genes in the DNA act as the template for making proteins. The cellular machinery that copies the DNA is very accurate, and there are proofreading mechanisms to ensure high fidelity. Yet still, there are 3 billion DNA bases in the human genome that must be copied and by chance some of these bases will not be accurately copied. The result is a DNA mutation.
Sometimes these mutations do not cause harm because not all sections of the DNA are equal. Some parts of the DNA are not used to encode genes, so the mutation will likely not affect the cell. Sometimes the mutation will occur in a part of the gene that is not essential for the protein’s function, thus it will not affect the cell. But occasionally, the mutation will affect a critical part of the gene that is essential to the proper function of the protein encoded by the gene. In this case, the protein may lose its function or adopt a new (possibly deleterious) function.
These DNA mutations occur naturally but also can be promoted by radiation, chemical carcinogens, or free radicals released in metabolic processes.
Some individuals have a higher risk of developing cancer due to a mutation carried in their family’s DNA. Everybody has two copies of each gene, one from their mother and one from their father. If an individual inherits one defective copy of a tumor suppressor gene from their parent, generally the other normal copy will be sufficient to perform the gene’s normal function. However, it will only take a single mutation in the normal copy of the gene to lose the gene’s function, thereby greatly increasing the individual’s risk of developing cancer.
Now that we’ve covered the basic tenants of cancer, I’ll talk more about the difficulty of preventing and curing it in my next post.