How Does Chemotherapy Kill Cancer Cells?

Instructor: Amanda Robb

Amanda holds a Masters in Science from Tufts Medical School in Cellular and Molecular Physiology. She has taught high school Biology and Physics for 8 years.

In this lesson, we'll be exploring how chemotherapy kills cancer cells. We'll also look at the effects of chemotherapy on healthy cells and side effects.

What Is Chemotherapy?

Picture working on the cancer floor in the hospital. Patients come in, often scared and disheartened. After the initial shock, you start discussing treatments with them. Not all cancers can be removed with surgery, and some will require systemic treatment. One of the more common treatments is chemotherapy. Chemotherapy involves administering drugs to prevent the reproduction of cancer cells. There are a variety of chemotherapy drugs that each have a different mechanism. However, the end goal is always the same: stop cancer cells from dividing. Before we get into how the drugs work, let's refresh about the cell cycle and how it gets unregulated during cancer.

The Cell Cycle

The cell cycle is the cycle of a cell's life. It includes phases where the cell rests, where it prepares for cell division, replicates DNA, and then divides. Normally there are strict checkpoints between each phase, like border patrol agents between different countries. Just like the patrol agents check that everyone is safe and documented before letting them proceed, the checkpoint proteins check that the cell is healthy and that DNA is intact before letting it go on.

Cell cycle checkpoints normally prevent unhealthy cells from dividing
checkpoints

If the DNA is damaged in any way, the cell pauses to fix it and moves on. If the DNA damage is too extensive, the cell takes drastic measures by going through apoptosis. In this process, the cell self-destructs to save the organism from any further damages.

So, what happens in cancer? Cancer occurs when a cell accumulates mutations in important proteins that control the cell cycle. The cell's checkpoints become broken and the cell speeds through the cell cycle out of control. Imagine if the border patrol agents just took a break and stopped checking passports at their post.

As the cell speeds through the cell cycle more and more mutations occur, the cell's behavior starts to change and it no longer does its job in the body. The cell divides out of control and steals space and nutrients from healthy cells.

Chemotherapy takes advantage of the mechanisms that trigger apoptosis. Chemotherapy drugs either interfere with the process of DNA replication, or directly damage the DNA so badly the cell must go through apoptosis, killing the cancer cells. However, chemotherapy drugs damage any cells that are actively going through cell division, not just cancer cells. Thus, cells that divide a lot, like our intestinal, skin, hair, and blood cells are also hurt by chemotherapy, producing harmful side effects.

Despite these side effects, chemotherapy drugs are widely used and do improve patient outcomes during cancer. There are several types of chemotherapy drugs, each with a different mechanism of action.

Types of Chemotherapy Drugs

Alkylating Agents

These drugs cause mutations in the DNA, which hopefully lead to apoptosis. An alkylating agent binds to DNA and causes structural changes that prevent the cell from replicating DNA. If a cell doesn't replicate DNA properly, it will stop the cell cycle and go through apoptosis. However, since these drugs affect all rapidly dividing cells, other healthy cells become casualties.

Antimetabolites

These drugs have a similar effect as alkylating agents, but go about their job in a different way. During DNA replication; the process of making more DNA before a cell divides, individual building blocks called nucleotides are linked together to form the new DNA. An antimetabolite looks like a nucleotide, but it has a slightly different shape that prevents DNA replication from occurring, thus stopping cell division. Imagine doing a puzzle. Each piece you grab will eventually fit the puzzle somewhere. Now imagine if you put two different puzzles together. Half of the pieces would not fit and grabbing the wrong pieces would prevent you from putting the puzzle together, just like antimetabolites prevent DNA replication.

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