Oncogenesis: The Process That Leads to Cancer

Oncogenesis is the complex, multi-step process by which normal cells turn into cancerous cells, leading to cancer growth in the body. It involves genetic changes in a group of cells that causes them to grow and behave abnormally.

The word is formed by "onco" (the Latin word for "tumor") and "genesis" meaning "beginning." “Tumorigenesis” is another term used for this process. Another word, “carcinogenesis,” means roughly the same thing, although it is sometimes used to refer to the earliest part of the process when tumor formation first begins.

To understand oncogenesis, it helps to understand what a cancer really is. Cancer is a name for a group of diseases that share some similarities but have some distinct differences, both in terms of the specific changes that have occurred and the possible treatment options. For instance, a breast cancer is different than a cancer arising from another part of the body, such as colon cancer.

However, even with cancer that occurs within a single organ, there are many different subtypes of cancer which may respond differently to treatments. There are many different types of breast cancer, and more subtypes will probably be discovered as scientists learn about the specific differences that can occur.

Cells are the small individual working units that compose the tissues and organs of your body. Each cell contains its own copy of DNA, the genetic material you inherit from your parents. Different cells have different purposes and do different jobs, depending on where in the body they are found. Inside every cell is the machinery it needs to copy its genetic material and divide to make a new "daughter" cell. But this should happen only under specific, controlled circumstances.

As an example, it’s normal for certain types of bone cells to grow and divide in children as they become taller. Cells in your skin normally replicate themselves as well, to replace the old, dead skin cells that are continuously shed. Certain immune cells should replicate themselves as part of your immune response to infection. But other cells in your body shouldn’t replicate and divide under normal circumstances. For example, muscle cells do not normally replicate themselves in adults.

Cancer can occur when a cell or group of cells begin to abnormally grow and divide in an unchecked way. Instead of dividing only when needed, they may begin to divide unnecessarily.

Then, daughter cells of the abnormal cells will share this same tendency to divide—this creates even more cells. In some cases, the cancer cells may invade other areas and interfere with the functions of normal cells. This can lead to the symptoms of the specific cancer, and it may cause death if untreated.

A very complicated system of signaling inside and outside cells triggers the process of replication (called mitosis). There are many checks and balances in place to make sure that cells don’t divide and replicate when and where they shouldn’t. There are many different important proteins that help regulate cell division—these are encoded by specific genes in your DNA. Other important proteins work to help your cell recognize when it is not working normally.

In certain circumstances, something may damage the DNA that encodes one of these important proteins. Sometimes, the cell manages to repair the DNA successfully without a problem. Other times, however, the DNA might not be correctly repaired, leading to what is known as a genetic mutation. This mutation is then passed down to every new daughter cell. The protein made from the mutated DNA may not work as it normally would.

Though it may not be a big issue at first, the cell may experience more damage to other important parts of the DNA—other genetic damages, or “hits.” A cancer occurs when a group of cells has lost a critical mass of these feedback mechanisms, and they are replicating themselves without proper cellular controls. This happens through the process of oncogenesis, which may occur over many years before a fully developed cancer is discovered. Other genetic hits may make the cancer even more dangerous by enabling it to better invade tissues or achieve a blood supply. Other genetic “hits” may prevent the cells from going through the normal processes of cellular death (called “apoptosis).

Some of the “hits” that occur are not due to changes in the DNA itself, but due to changes in molecules attached to the DNA or to its packing material. These are called “epigenetic” changes. For example, the addition of a molecule at a specific location might increase how often a specific gene is made into a protein. Or it might do the reverse. Depending on the gene involved, this might contribute to the process of oncogenesis.

Through this complex process, the cancer tissue is prone to invade nearby tissue, which may impair its function. It also may metastasize. That means, that the cancerous cells can spread through the blood or lymph system and start to grow in other parts of the body, like the lungs or the liver. 

One important characteristic of a true cancer is this ability to invade nearby tissue or potentially metastasize throughout the body.

Benign tumors share some characteristics with cancer. They may have picked up some genetic “hits” that cause them to behave a little differently than normal tissue. They may also divide in some uncontrolled ways. However, they do not have as many severe genetic and epigenetic hits as a cancer. By definition, a benign tumor is not prone to massive spread in the body. In rare circumstances, a benign tumor goes on to become a malignant one, a true cancer, but usually, this doesn’t happen. However, some benign tumors still sometimes cause problems. This might happen, for example, if one was pressing on a nearby important blood vessel. 

Cancers are a complex group of diseases with a complicated set of causes. Anything that can damage the DNA or cause certain epigenetic changes can increase one’s risk of getting cancer.

Such substances that can damage the DNA are called carcinogens. DNA damage to specific genes can lead to the process of oncogenesis. For example, excess exposure to ionizing radiation from the sun can increase one’s risk of getting skin cancer. Exposure to DNA-damaging substances in cigarettes can increase one’s risk of lung and other cancers. Certain substances don’t cause direct DNA damage, but instead, alter the epigenetic coding in a way that makes cancer more likely.

In most cases, it’s thought that a variety of factors must come together to cause a cancer. In other words, a person must experience more than one genetic or epigenetic alteration to develop the disease. By the time a cell is cancerous, it has acquired a number of genetic mutations that it continues to pass on to its daughter cells as it divides.

Factors that stress cells and disrupt normal cellular function can also increase one’s risk of cancer. For example, in people with gastroesophageal reflux disease, certain cells in the esophagus are exposed to acid from the stomach. This can lead to dysplasia, a pre-cancerous condition in which cells are not quite behaving normally but aren’t yet acting like fully developed cancer cells. These cells sometimes, but not always, go on to develop a cancer. There is growing evidence that this and other kinds of chronic inflammation may increase one’s risk of cancer as well.

Infection with certain types of viruses can also increase one’s risk of cancer, though not everyone with the virus will develop it. These viruses can insert genetic material into normal cells that can contribute to cancer development. In other cases, they may disrupt the immune system, thus increasing one’s risk of cancer.

One’s family history is also an important factor. People who have inherited certain genes from their parents are more susceptible to getting cancer. That’s because certain variants of particular genes may be more susceptible to cancer formation. For example, the BRCA gene makes a protein that is important for normal DNA repair. People born with certain variations of this gene may be more likely to develop certain types of cancers compared to people who don’t have the mutated version.

Age is also a major risk factor. Except for certain cancers that almost always occur in children, the risk of most cancers increases with age. That’s because people normally accumulate mutations in their genes over time. With greater age, there is an increased risk that one of your cells will get enough of the wrong kind of “hit” to get cancer. 

It’s important to note that some people get cancer even if they don’t have a family history of cancer, and even if they aren’t exposed to any known major carcinogens.

Generally speaking, one can decrease the risk of cancer by lowering one’s exposure to these possible genetic and epigenetic “hits.”

Certain screening procedures can also make sure that precancerous areas of the body are detected early when they are easily removed.

Oncogenesis has already occurred in people diagnosed with cancer, and this process cannot be reversed. Many types of cancer treatments focus on removing cancerous cells from the body. For example, a surgeon may be able to remove all cancerous cells from the body, curing the person of the disease. Other treatments, like chemotherapy, may focus on killing the cancerous cells. Such treatments don’t work by stopping oncogenesis, but by removing cancerous cells from the body completely.

However, other types of cancer treatments prevent cancerous cells from being as dangerous to the body. For example, certain treatments stop the cancer's ability to form new blood vessels (angiogenesis). Other treatments may slow a cancer’s growth in other ways. By slowing the cancer’s growth, they may help the cancer from getting further genetic hits that might make it more difficult to treat. In this sense, these treatments may slow or even stop the process of oncogenesis. However, most people will also need other treatments that directly remove the cancer from the body.