Emily Poulin, PhD
Emily is a cancer biologist and science communicator and  has always been fascinated by the simple, yet incredibly complex nature of biology.

Emily Poulin, PhD
Emily is a cancer biologist and science communicator and  has always been fascinated by the simple, yet incredibly complex nature of biology.

Cancer is a disease that affects so many of us, directly or indirectly. But what is cancer exactly and what can we do to protect ourselves against it?

What is cancer?

At its root, cancer occurs when cells of the body lose normal control of growth and death. Normal cells are under strict controls that determine if and when a cell divides (or proliferates) and if and when it dies. When these controls are undermined, a cell may proliferate when it is not supposed to or evade cell death when it should die. The result of these scenarios is the accumulation of abnormal cells that have a survival advantage over surrounding normal cells.

Why does cancer happen?

Environmental factors can cause mutations

The dysregulation of normal cell proliferation and cell death in cancer is a result of genetic mutations, or changes to a cell’s DNA sequence. Environmental factors or mistakes that occur during DNA replication can cause mutations. For example, ultraviolet (UV) irradiation from the sun may cause mutations in skin cells that over time, can lead to skin cancer. 

Non-inherited mutations are naturally acquired throughout life, both through the environment (like UV irradiation from the sun) or through the normal process of cell division. Each time a cell divides, its DNA must be replicated. During this process, mistakes can be made, and mutations may be introduced. Although our cells have dedicated DNA repair mechanisms that check for such DNA replication errors, mutations may sneak by and be entered into the DNA of the next generation of cells.

Molting blue to orange DNA double stand represented evolution or mutant, 3D rendered
Each time a cell divides, its DNA must be replicated. During this process, mistakes can be made, and mutations may be introduced.

Mutations can be inherited

Inherited cancer-causing mutations are responsible for certain types of hereditary cancers. Mutations in the BRCA1 and BRCA2 genes are well known to increase the risk of breast or ovarian cancer. Inherited mutations in BRCA1 and BRCA2 are responsible for approximately 3% of breast cancers and 10% of ovarian cancers.

Some genes protect us from cancer

Not every mutation will lead to cancer. There are some genes that are particularly important for regulating cell growth and death and the normal function of these genes protects us against cancer. 

The two major types of genes that are implicated in cancer are called tumor suppressor genes and oncogenes. Tumor suppressor genes typically play a role in turning off cell growth and proliferation and inducing cell death. In contrast, oncogenes are responsible for promoting cell growth and proliferation. Normally, the activity of oncogenes is tightly controlled so that they are not activated inappropriately, causing unregulated growth and proliferation. 

Mutations that affect the activity of tumor suppressor genes and oncogenes promote cancer development. In particular, cancer-inducing mutations inactivate tumor suppressor genes and activate oncogenes. In this way, the anti-cancer protective measures that tumor suppressors offer are lost and the fine control over oncogenes leaves their activity unchecked. The combination of tumor suppressor loss and oncogene activation causes the perfect storm for the initiation of cancer development.

What about the immune system’s role in cancer development?

The involvement of the immune system in the process of cancer development has been well known for over a century and the evasion of the immune system is now considered to be one of the hallmarks of cancer

The immune system can both hinder and promote the spread of cancer cells.

Normally,  the immune system identifies and destroys cancer cells. However, if not all of the abnormal cells are destroyed, a state of equilibrium evolves in which the immune system keeps cancer cell growth and proliferation in check and the cancer cells remain dormant. However, cancer cells are still present and may eventually evolve to escape the dormancy imposed by the immune system.

If the immune system loses the ability to recognize cancer cells, they can  hide in plain sight. Once immune escape occurs, cancer cells may proliferate in an uncontrolled manner, promoting tumor progression. This process through which the immune system can both prevent and stimulate cancer spread is known as immunoediting, and it highlights the role of the immune system in cancer pathogenesis. 

Cancer cell attacked by Lymphocytes
Cancer cell attacked by cells of the immune system. Normally,  the immune system identifies and destroys cancer cells. However, cancer cells can learn to evade the immune system and go undetected.

The immune system uses ‘immune checkpoints’ to distinguish between normal cells and cancer cells

The immune system is responsible for finding and destroying foreign cells in the body while leaving normal cells unscathed. One of the methods immune cells use to distinguish normal cells from foreign cells—or cancer cells—is the immune checkpoint. Normal cells have proteins on their surface that bind to specialized proteins on T cells called checkpoint proteins. This binding process flags to the T cells that these cells are “normal” or “self” and should not be destroyed. Foreign cells do not display proteins recognized by checkpoint proteins and are therefore targeted for destruction. One of the ways in which some cancers have evolved to evade the immune system is by expressing these checkpoint protein binding proteins on their surface, essentially, turning on an immune disguise and evading immune detection.

Immune checkpoint inhibitors reveal cancer cells to the immune system  

Immune checkpoint inhibitors are anti-cancer drugs that act by blocking the binding of T cell checkpoint proteins with the proteins they recognize on the surface of other cells. These drugs inhibit the immune checkpoint process, revealing cancer cells to the immune system and stimulating their destruction. One example of a checkpoint protein is PD-1, which is expressed on T cells and recognizes and binds to PD-L1 on the surface of normal cells. Cancer cells that have high levels of PD-L1 are able to evade immune destruction by appearing to T cells as normal cells. PD-1 and PD-L1 inhibitors are being investigated as treatment options for multiple types of cancer, including rectal cancer. 

Rectal cancer disappears after treatment with an immune checkpoint inhibitor

Immune checkpoint inhibitor therapy is proving to be a successful approach to treating cancer. In a recent study published in the New England Journal of Medicine, investigators reported that rectal cancer disappeared in 12 patients who received the anti-PD-1 blocking antibody dostarlimab. This phase 2 study was conducted in people with locally advanced rectal cancer at Memorial Sloan Kettering Cancer Center and Yale University School of Medicine.  

This therapy was successful without the need for radiation, surgery, or chemotherapy — and the patients have been cancer-free for two years.

Is there anything we can do to lower the risk of cancer?

As we age, the risk of developing cancer increases; the median age of cancer diagnosis as of March 2021 was 66 years. Mutations accumulate over time, and the longer we live, the greater the chances of mutations occurring, either via environmental exposure or errors in DNA replication. However, long-term prevention strategies such as maintaining a healthy weight through diet and lifestyle and avoiding tobacco use may reduce the risk of developing cancer. Of note, lung cancer remains the most common cause of cancer-related deaths and about 80% of all lung cancers in the United States are due to tobacco use, demonstrating that lifestyle choices play a significant role in developing cancer.

Additionally, it is important to keep up with regular cancer screenings as appropriate. These may include a skin exam, colonoscopy, pap test, and mammography, to name a few. Staying current with cancer screenings increases the chances that if cancer is present, it will be identified early. Cancers that are found in early stages (before they spread to other parts of the body) may be easier to treat and as a result, have a better prognosis.  

Although cancer has continued to be a significant health problem, over the past decades, we have accumulated a wealth of knowledge about how cancer develops, how it can be treated, and how it can be caught early. As an indication of all we have learned and implemented, cancer-related deaths have decreased 27% from 2001 to 2020. With continued advances in health care and cancer research, this number will hopefully continue to decrease over time.