How does chemotherapy work?

During World War I, one of the

horrors of trench warfare was a poisonous yellow cloud

called mustard gas. For those unlucky enough to be exposed, it made the air impossible to breathe,

burned their eyes, and caused huge blisters on exposed skin. Scientists tried desperately to develop an

antidote to this vicious weapon of war. In the process they discovered the gas

was irrevocably damaging the bone marrow of affected soldiers— halting its

ability to make blood cells. Despite these awful effects,

it gave scientists an idea. Cancer cells share a characteristic with

bone marrow: both replicate rapidly. So could one of the atrocities of war become a champion in the

fight against cancer? Researchers in the 1930s

investigated this idea by injecting compounds derived

from mustard gas into the veins of cancer patients. It took time and trial and error to find

treatments that did more good than harm, but by the end of World War II, they discovered what became known

as the first chemotherapy drugs. Today, there are more than 100. Chemotherapy drugs are delivered

through pills and injections and use "cytotoxic agents," which means

compounds that are toxic to living cells. Essentially, these medicines cause some

level of harm to all cells in the body— even healthy ones. But they reserve their most powerful

effects for rapidly-dividing cells, which is precisely the hallmark of cancer. Take, for example, those first

chemotherapy drugs, which are still used today and

are called alkylating agents. They’re injected into the bloodstream, which delivers them to

cells all over the body. Once inside, when the cell exposes

its DNA in order to copy it, they damage the building blocks of

DNA’s double helix structure, which can lead to cell death unless

the damage is repaired. Because cancer cells multiply rapidly, they take in a high concentration

of alkylating agents, and their DNA is frequently exposed

and rarely repaired. So they die off more often

than most other cells, which have time to fix damaged DNA and don’t accumulate the same

concentrations of alkylating agents. Another form of chemotherapy involves

compounds called microtubule stabilizers. Cells have small tubes that assemble

to help with cell division and DNA replication, then break back down. When microtubule stabilizers

get inside a cell, they keep those tiny tubes

from disassembling. That prevents the cell from completing

its replication, leading to its death. These are just two examples of the six

classes of chemotherapy drugs we use to treat cancer today. But despite its huge benefits,

chemotherapy has one big disadvantage: it affects other healthy cells in the body

that naturally have to renew rapidly. Hair follicles, the cells of the mouth,

the gastrointestinal lining, the reproductive system, and bone marrow

are hit nearly as hard as cancer. Similar to cancer cells, the rapid

production of these normal cells means that they’re reaching for

resources more frequently— and are therefore more exposed to

the effects of chemo drugs. That leads to several common side

effects of chemotherapy, including hair loss, fatigue, infertility,

nausea, and vomiting. Doctors commonly prescribe options

to help manage these side-effects, such as strong anti-nausea medications. For hair loss, devices called cold caps

can help lower the temperature around the head and

constrict blood vessels, limiting the amount of chemotherapy

drugs that reach hair follicles. And once a course of chemo

treatment is over, the healthy tissues that’ve been badly

affected by the drug will recover and begin to renew as usual. In 2018 alone, over 17 million people

world-wide received a cancer diagnosis. But chemotherapy and other treatments

have changed the outlook for so many. Just take the fact that up to 95% of

individuals with testicular cancer survive it, thanks to advances

in treatment. Even in people with acute myeloid

leukemia— an aggressive blood cancer— chemotherapy puts an estimated

60% of patients under 60 into remission following their

first phase of treatment. Researchers are still developing

more precise interventions that only target the intended

cancer cells. That’ll help improve survival rates

while leaving healthy tissues with reduced harm, making one of the best tools we have

in the fight against cancer even better.