What is chemotherapy?
To borrow a well known advertising phrase, chemotherapy does exactly what it says on the tin. Chemo – means to do with chemicals, or chemistry, therapy comes from a Greek word for healing. So chemotherapy literally means healing with chemicals. The word has been around for over a hundred years, and could be used for any medicine, but since the 1950s it has been mostly used for the drugs used to treat cancer. Today most people just call it “chemo”.
Humanity has been trying to treat cancer for a very long time. Records from ancient Egypt, ancient Greece and even Saxon England describe cancer and our early attempts to treat it. For thousands of years we made very little progress.
By the time of the first world war, in spite of testing virtually every known plant, animal and chemical substance, cancer was still an incurable disease. It was a chance observation made about survivors of one of the most horrific weapons of the war that really began the story of modern chemotherapy.
It turned out that mustard gas affected the bone marrow of people exposed to it, reducing the number of blood cells. It did this by damaging the DNA of rapidly dividing cells such as white blood cells causing them to die.
If mustard gas could kill rapidly dividing cells, could it kill cancer cells which also divide very quickly? The answer was yes.
After more research, including studies made of people accidentally poisoned by mustard gas in WWII proper trials of nitrogen mustards began in the late 1940s. By the late 1960s other chemicals such as methotrexate and vincristine had been shown to reduce the size of tumours, remission was possible and finally the dream of a cure was in sight. Today there are more than 100 chemotherapy drugs available for use, including a close relative of mustard gas, mechlorethamine.
The drugs that are used for chemotherapy are cytotoxic. Another word that describes what it does – cyto means cell, toxic means poisonous. They are all poisonous to cells because they affect the ability of a cell to divide.
Cell division is a normal, essential activity where your body makes new cells for growth or to replace damaged or worn out cells throughout your life. When a cell becomes cancerous it will divide uncontrollably. When a cell divides, it starts by growing, making more of all its internal parts so there’s enough for both of the new cells at the end. One of the most important things to be doubled is the DNA, the genetic material that codes the instructions for everything a cell makes and does which then needs to be shared equally between the two new cells. (For more information on DNA and the cell cycle see our other information pages). Cytotoxic chemotherapy drugs will damage some part of the DNA copying and dividing process which eventually leads to that cell dying.
Because many normal cells such as the ones lining your gut or your white blood cells are dividing, chemotherapy can damage them as well. This is one of the reasons for the side effects patients experience. The good news is that normal cells are more able to repair the damage and survive. Cancer cells will not be able to repair themselves and instead self-destruct by a process known as apoptosis and die.
There are five different groups of drugs which all affect cell division in different ways. They are often combined because together they are often more effective than a single drug.
Mitotic Inhibitors/ plant alkaloids
Mitosis is the word biologists use to describe the process where a cell shares its DNA equally before dividing into two new cells. First the DNA gets packaged up into large structures called chromosomes, for easy transport. The cell attaches microscopic chains that grow and shrink, dragging the chromosomes into two identical groups before the cell finally divides.
Chemotherapy drugs such as vinblastine, paclitaxel (taxol) and eribulin damage these chains, so the division process can’t be completed. They are particularly unusual because they were originally found in nature – taxol from pacific yew trees and eribulin from a sea sponge. Which is why they are also called plant alkaloids.
These are best described as chemicals that react directly with DNA, chemically attaching nearby parts of the DNA molecule together. A bit like a molecular staple or glue.
These “glued” bits of DNA make it impossible for a cell to copy its DNA ready for division, cell division stops and if the cell can’t repair the damage they die.
This family includes mustard gas and drugs used today such as cisplatin and carboplatin.
Have you ever created a horrible twisted mess by trying to separate individual threads from a ball of wool by pulling the ends apart, or had the electric cable on a tool twist itself into knots if you keep turning it in the same direction? Because DNA is a long, twisted molecule when it gets copied the same can happen. Cells have something called topoisomerases that untangle DNA by breaking and rejoining it. Drugs that interfere with this are called topoisomerase inhibitors. If the cell can’t untwist its DNA it gets permanently damaged and the cell eventually dies.
These drugs are chemical imposters! They are very similar to the chemical building blocks of DNA. They work in two ways. The first is by swamping the DNA copying machinery with parts that are not quite right, slowing it down. The second is when DNA is copied. The copy is made by inserting new building blocks into a growing chain. If one of these is an imposter molecule it will stop the copying process as the next part won’t fit properly. As with the other types of chemo, this eventually leads to the cells dying.
Antibiotics are normally associated with treating bacterial infections. Bleomycin and doxorubicin (adriamycin) originally came from the streptomyces bacteria where they are naturally produced. They are similar to some of the other drugs because they also interfere with the ability of the cell to manage the twisting of DNA when it is copied.
New targeted medicines and immunotherapy
Although conventional chemotherapy drugs are highly effective and have cured or slowed many cancers they have a lot of problems. Many of the unpleasant side-effects are caused by damaging normal cells that are dividing. Researchers have been developing smarter ways of killing cancer cells that rely on unique features that the cancer cells have developed. These usually have fewer side effects and are more effective. For more information see our other articles…