Chemotherapy is a standard part of treatment for many types of cancer. It involves drugs that contain chemicals to kill cancer cells. Each class of chemotherapy drugs destroys cancer cells in different ways.

Antimetabolites are one of the oldest and most common types of chemotherapy drugs. They work by mimicking molecules cancer cells need to replicate their genetic information and interfering with their ability to replicate.

In this article, we break down everything you need to know about using antimetabolite medications to treat cancer. You will learn about how they work, what types of cancer they’re used to treat, and potential side effects.

Antimetabolites are a type of chemotherapy drug and have been used in cancer treatment for about 70 years. They remain one of the most common treatments for cancer.

To understand how antimetabolite drugs work, it helps to know how cells store their genetic information.

DNA structure of cancer cells

Every cell, including cancer cells, contains DNA, which provides instructions the cell needs to survive and replicate itself.

DNA is made up of two long strands of molecules that spiral around each other in a shape called a double helix. Each strand is made up of alternating sugar and phosphate molecules. One of four types of base molecules are attached to each sugar molecule.

These bases are called:

  • adenine
  • cytosine
  • guanine
  • thymine

Adenine and guanine are known as purines. Thymine and cytosine are known as pyrimidines. The pattern of these four molecules along the strand of DNA creates specific instructions on how the cell can create proteins and other important molecules called RNA.

You can think of each of these molecules as individual letters in a sentence. Individually, they’re meaningless. But put together, they can create complex messages.

How antimetabolites interfere with cancer replication

Antimetabolite drugs are structurally similar to purines, pyrimidines, or other essential molecules cancer cells need to build their DNA.

When cancer cells use antimetabolites instead of the primary molecules to build their genetic information, they are not able to properly create the enzymes they need to divide. Then the cancer cells die.

For example, a commonly used antimetabolite drug called 5-fluorouracil targets the enzyme thymidylate synthetase and interferes with cancer cells’ ability to create pyrimidines.

Cancer cells often develop resistance to antimetabolites over time, which has led scientists to develop new types of antimetabolites that target cancer in different ways. At least 17 types of antimetabolites are FDA-approved in the United States.

Antimetabolites can be divided into subcategories, depending on what type of molecules they mimic:

  • Folic acid analogs. These disrupt the enzyme called dihydrofolate reductase, which is needed to convert folic acid to the molecule tetrahydrofolate. This interferes with DNA and RNA synthesis inside a cancer cell.
  • Pyrimidine analogs. These are molecules that closely resemble the pyrimidines cytosine and uracil, which cancer cells need to create DNA and RNA.
  • Purine analogs. These molecules closely resemble the purines adenine and guanine, which cancer cells need to create DNA and RNA.

Antimetabolites are commonly used to treat:

They’re also used to treat many other types of cancer. Here’s a look at some antimetabolites with examples of the types of cancer they’re used to treat.

Drug nameExample uses
5-fluorouracilskin cancer, colorectal cancer, breast cancer
6-mercaptopurineacute lymphoblastic leukemia
azacitidineacute myeloid leukemia
capecitabinecolorectal cancer, esophageal cancer, pancreatic cancer
thioguanineacute myeloid leukemia
decitabinemyelodysplastic syndrome
cytarabineacute lymphocytic leukemia, acute promyelocytic leukemia, acute myeloid leukemia
pemetrexednon-small cell lung cancer
nelarabineT-cell acute lymphoblastic leukemia, T-cell lymphoblastic lymphoma
methotrexateacute lymphoblastic leukemia, non-Hodgkin’s lymphoma, breast cancer
hydroxyureachronic myeloid leukemia, melanoma, head and neck cancers
fludarabinechronic lymphocytic leukemia, non-Hodgkin’s lymphoma, acute leukemias
gemcitabinepancreas cancer, bladder cancer, non-small cell lung cancer
clofarabineacute lymphoblastic leukemia
floxuridinecolon cancer, kidney cancer, stomach cancer
pralatrexateperipheral T-cell lymphoma
pentostatinT-cell prolymphocytic leukemia, chronic lymphocytic leukemia, cutaneous T-cell lymphomas
trifluridine/tipiracil combinationcolorectal cancer
cladribinehairy cell leukemia, acute myeloid leukemia, chronic lymphocytic leukemia

Many types of antimetabolites and other chemotherapy drugs are delivered intravenously (IV). This means they go directly into your vein.

According to the American Cancer Society, these drugs are put directly into your bloodstream with a plastic tube called a catheter. A medical expert will put the catheter into a vein in your forearm or hand with a needle.

There are three ways that these drugs are administered:

  • IV push. The drugs are delivered into the catheter through a syringe over several minutes.
  • IV infusion. The drugs flow from a plastic bag filled with a mixed drug solution and through a tube. They go into your catheter over the course of minutes to hours.
  • Continuous infusion. An infusion flows through your catheter over the course of a day or several days.

In some cases, antimetabolites may be delivered through a central venous catheter, which is a larger catheter that’s put into one of the large veins in your chest.

In order to treat cancers of your brain or spinal cord, you may receive chemotherapy drugs directly into your spinal cord through a lumbar puncture. Chemotherapy drugs are also administered this way to prevent leukemias and some other types of cancer from spreading to your central nervous system.

Some antimetabolites are available as topical creams to treat skin cancer. For example, 5-fluorouracil is available in 0.5- to 5-percent creams.

Some antimetabolites are also available in oral forms that you can take by mouth. For example, the drug 6-mercaptopurine comes in 50-milligram tablets.

Antimetabolites can kill cancer cells, shrink tumors, slow cancer growth, and potentially lead to remission. Remission is when doctors cannot detect any signs of your cancer.

People’s bodies often tolerate antimetabolites well. These types of chemotherapy drugs cause a remarkable response to advanced-stage cancer, often leading to complete remission.

Along with treating cancer, some types of antimetabolites can treat other conditions, such as rheumatoid arthritis.

Chemotherapy is an important part of treatment for a wide variety of cancers. But chemicals in chemotherapy medications can also damage healthy cells in your body.

Chemicals in chemotherapy drugs tend to affect cells that divide quickly, such as those found in your:

  • bone marrow
  • digestive system
  • reproductive system
  • hair follicles

Damage to these types of cells can cause you to experience a wide variety of side effects.

Major side effects of antimetabolites may occur in your gastrointestinal system and cells that produce blood.

You should not take antimetabolites if you’re breastfeeding due to potential toxicity to your child, unless your doctor says it’s okay.

Antimetabolites can cause a wide range of side effects that vary between drugs. Some general side effects include:

When applied topically, antimetabolites can cause skin symptoms such as:

  • skin irritation
  • sores
  • infection
  • pain
  • redness
  • crusting
  • itchiness
  • rash

Antimetabolites are sometimes used in combination with other treatments, such as radiation therapy or surgery. If taking antimetabolites does not get rid of your cancer, your doctor may suggest alternative treatment options.

Other treatment options include:

Antimetabolites are a group of chemotherapy drugs that mimic molecules that cancer cells need to create their DNA. When cancer cells use antimetabolites in their DNA, the drugs interfere with their ability to replicate properly. Then the cancer cells die.

Antimetabolites are effective at treating many types of cancer. Like all types of chemotherapy, they can cause damage to healthy cells that leads to side effects like nausea, vomiting, and hair loss.

If you or your loved one has cancer, your doctor may recommend taking antimetabolites or other forms of chemotherapy. Discussing the potential benefits and risks with your doctor can give you the best idea of what to expect and your outlook.