How Do Chemotherapy Drugs Fight Cancer?

drugs target dna, genetic base pairs in many different ways

By Jonny Lupsha, Wondrium Staff Writer

There are several ways to treat cancer, including radiation and drugs. Some drugs attack DNA and some attack other cell processes in order to fight cancer. How do chemotherapy drugs work?

Helix human DNA structure
Chemotherapy drugs circulate throughout the body in the bloodstream as systemic treatment to stop or slow the growth of cancer cells. Photo by james benjamin / Shutterstock

Between 1.8 and 1.9 million Americans are diagnosed with cancer every year. Tragically, cancer is often fatal and humanity has yet to discover a catch-all cure or a cure with a 100% success rate, although science and medicine are always advancing. In fact, some cancer-treating chemotherapy drugs are successful enough that the United States is currently facing a shortage of them.

The United States often relies on India and China for manufactured medicines and individual drug ingredients. A drug supply breakdown is only exacerbating the low shortage of chemotherapy drugs like cisplatin. But how do drugs fight cancer? In his video series What Science Knows about Cancer, Dr. David Sadava, Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center in Duarte, CA, goes inside the body to examine cancer treatment.

How Do Chemotherapy Drugs Work?

“The growth of a cancer cell population is composed of two parameters,” Dr. Sadava said. “Births, that is the cell division producing new cells, and deaths, cells dying, either being killed by the drug or going into programmed cell death.”

The technical term for drugs that stop cells from dividing is “cytostatic,” while the term for drugs that facilitate cells into a programmed cell death is “cytotoxic.” According to Dr. Sadava, drugs that target DNA do one of two things: They either target the building blocks of DNA—the bases adenine (A), cytosine (C), guanine (G), and thymine (T)—or they target the DNA structure itself.

First, there are the drugs that target the bases. One popular method is to stop the conversion of molecules within the cell into the base thymine. Why thymine? If scientists can do that, they can stop cell division and reproduction. They do so with a drug called methotrexate.

“If you stop that conversion, there’s no methyl group there,” Dr. Sadava said. “When the reaction tries to happen, it can’t; you can’t make T, and it dies, what scientists call a thymine-less death.”

This happens because methotrexate is a molecule created in a lab to look like folic acid, which ordinarily gets converted by an enzyme for cell division. When methotrexate is introduced, the enzyme binds to it instead, freezing the reaction and stopping cancer cell division.

How Do Drugs Attack DNA?

The second method of drugs targeting DNA is to attack the DNA structure itself. How does this work? In order for DNA to function, its two strands have to separate. One way to prevent its function is to stop that separation.

“The DNA is really, really a mess,” Dr. Sadava said. “It’s a big plate of pasta. To make the DNA available, a region of DNA available for duplication of DNA or expression, we got to dig way into that pasta, and get a small piece, and get it up to the surface. How do you unknot something inside the cell? […] Have one strand pass through the other to kind of undo it.”

This is done by an enzyme called topoisomerase. In order to stop topoisomerase in its tracks, a drug called etoposide is used to freeze the the mechanism. Once etoposide is introduced, the DNA remains a large, knotted mess and goes into programmed cell death.

The current cancer drug shortage includes cisplatin. Cisplatin performs a different but similarly effective function. According to Dr. Sadava, cisplatin performs similar to mustine, a drug derived from mustard gas. Mustine crosslinks DNA.

“The [DNA] strands have to separate; they have to unwind,” Dr. Sadava said. “To unwind the strands, you have to have them available to unwind, but if they’re glued together, tough luck. So cisplatin does that, essentially glues them together. Again, the cell will go into programmed death because it can’t duplicate or express its DNA.”

What Science Knows about Cancer is now available to stream on Wondrium.

Edited by Angela Shoemaker, Wondrium Daily