How Does Chemo Work?

The Cell Cycle

The purpose of chemotherapy is to restrict processes within the human body that allow for cancer cell division and reproduction. This goal is attained through a number of different methods with a number of different chemotherapy drugs. In fact, chemotherapy drugs are often divided into categories based on how they work, their interaction with other drugs as well as their chemical composition and structure. Understanding the unique properties and side effects of these substances allows oncologists to predict the drugs that should and should not be used together as well as proper, safe dosage levels (Different Types of Chemotherapy Drugs). 

Cancer cells grow and divide in much the same way as other cells in the human body; they must follow the generic cell cycle. There are five stages involved in the cell cycle:

G0: Resting Phase - the cell is not dividing
G1: Enzyme duplication occurs - the cell begins the division process by creating enzymes vital for cell division
S: DNA duplication occurs 
G2: Cell prepares to divide - This phase is similar to a checkpoint for cells to ensure that proper DNA duplication has occurred
M: Cell finally divides into two daughter cells

Depending on the type (or class) of chemotherapy drugs, different phases of the cell cycle will be acted upon in order to stop cancer cell division. The following paragraphs describe the most common categories of these drugs, as well as their functions in terms of cancer cell growth restriction.

1. Alkylating Agents: Alkylating agents bind to a cell’s DNA to halt its division (Your Guide to Cancer Care). When alkylating agents react with a cancer cell's DNA, they add alkyl groups to one or more DNA molecules. This addition of alkyl groups causes disturbances and changes in the sensitive double helix structure of DNA. The DNA strands break apart, and eventually, the cancerous cell dies (Types of Chemotherapy Agents and Regimens). These drugs work in all phases of the cell cycle and are used to treat a variety of different cancers including leukemia, lymphoma, Hodgkin disease, lung cancer and breast cancer. Since these drugs destroy cell DNA, they may cause long-term damage to the bone marrow, which, in rare cases, may lead to acute leukemia five to ten years after treatment (Different Types of Chemotherapy Drugs). An alkylating agent, mechlorethamine, is often used to treat Hodgkin's disease (Types of Chemotherapy Agents and Regimens). 

2. Platinum Drugs: Platinum drugs function very much like the alkylating agents and include substances such as cisplatin, carboplatin and oxalaplatin. They, too, work to kill cancerous cells. What gives them their own, unique group, however, is that unlike alkylating agents, platinum drugs are less likely to cause leukemia in the future (Different Types of Chemotherapy Drugs).

Cancer Cell being acted upon by Topoisomerase inhibitors, Alkylating
agents and Antimetabolites

3. Antimetabolites:  Each enzyme binds to a different “substrate”.  These “substrates” or reactants in a biological reaction fit perfectly into the groove (formally known as the active site) of an enzyme. Enzymes can then catalyze the reaction and assist in the production of the reaction’s products. Antimetabolites interfere with enzymes vital for DNA synthesis. Each antimetabolite is structurally similar to its enzyme’s substrate and, due to the structural similarity, can bind easily to its enzyme. However, these antimetabolites do not react the same way with enzymes as would the original substrate; oftentimes, “the enzymatic reaction is inhibited” (Antimetabolite). Antimetabolites work during the S phase of the cell cycle. They may be used to treat cancers such as leukemia, breast cancer, cancers of the ovary, intestinal cancers as well as other types of cancers. Some examples of antimetabolite drugs include: 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), and Capecitabine (Different Types of Chemotherapy Drugs). 

Chemotherapy Drugs

4. Antitumor Antibiotics: These drugs work in all stages of the cell cycle (Different Types of Chemotherapy Drugs); DNA uncoiling is prevented and DNA structure is altered, thereby stopping cell reproduction as well as killing the cancer cells. One form of antitumor antibiotics includes anthracyclines. Though anthracyclines are essentially named antibiotics, they are very different from the antibiotics used against bacterial infections! Anthracyclines interfere with enzymes involved in DNA replication and can be used to treat numerous types of cancers. However,  this type of antitumor antibiotic can cause permanent damage to the heart if dosage is not controlled or exceeds an amount deemed safe. As a result, anthracyclines often have “lifetime dose limits” placed upon them. Some examples of anthracyclines include Daunorubicin, Epirubicin and Idarubicin (Different Types of Chemotherapy Drugs).

5. Topoisomerase Inhibitors: interfere with enzymes (called topoisomerases) that separate the strands of DNA so that they can be copied. They may be used to treat leukemia, and lung, ovarian and gastrointestinal cancers. Two Topoisomerase inhibitors exist: topoisomerase l and topoisomerase ll

• Topoisomerase l (derived from camptothecin, a plant extract) examples: topotecan and irinotecan (Topoisomerase l Inhibitors)
• Topoisomerase ll examples: etoposide and teniposide

Treatment using topoisomerase ll increases the risk of getting acute myelogenous leukemia two or three years after the drug is administered.

6.Hormonal drugs/Corticosteroids: Some hormones encourage cancer cell growth. Hormonal drugs suppress these hormone processes (Your Guide to Cancer Care). Corticosteroids can be used to treat a number of different cancers such as lymphoma, leukemia and multiple myeloma. They can also be used to treat other illnesses. However, they are considered chemotherapy drugs only when they are used to kill cancerous cells. Corticosteroids are also used as anti-emetics to guard against vomiting and nausea that may be caused by chemotherapy, and to prevent allergic reactions. However, when used for these purposes, corticosteroids are not considered chemotherapy drugs (Different Types of Chemotherapy Drugs).

7. Plant Alkaloids/Mitotic Inhibitors: Plant alkaloids alter the interior structure of the cancer cell to stop cell division. (Your Guide to Cancer Care). Plant alkaloids are also called mitotic inhibitors. Plant alkaloids “inhibit enzymes from making proteins needed for cell division” (Different Types of Chemotherapy Drugs). These drugs work during the M phase of the cell cycle but cause damage to the cell in all phases of the cell cycle. Plant alkaloids can be used to treat a number of different cancers including breast cancer, lymphomas, and leukemia (Different Types of Chemotherapy Drugs). Like anthracyclines, plant alkaloids can have dangerous side effects from overuse (such as peripheral nerve damage) as a result of which dosage must be restricted. Examples of plant alkaloids include: Taxanes, Epothilones, and Estramustine. 

For a summary of some of these common chemotherapy drugs, please refer to the video below: