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The history of chemotherapy

PillsThe underlying principle of chemotherapy is to kill the cancer by treating them with chemicals that interfere with the process of cell division. They do this either by damaging the proteins involved, or by damaging the DNA itself. This causes the damaged cells to commit suicide (by apoptosis).

Chemotherapy drugs are effective against cancer cells because these cells divide rapidly, whereas most normal cells in your body do not. However, some cells in your body, such as bone marrow cells, immune cells and hair follicle cells also divide rapidly and are often damaged during chemotherapy. As a result, chemotherapy drugs often have unpleasant side effects such as nausea, hair loss and vomiting.

Modern-day chemotherapy has its origins on the battlefields of the First World War. Military doctors noticed that soldiers exposed to mustard gas, a chemical warfare agent, died because their bone marrow was destroyed (a condition called 'bone marrow aplasia'). Doctors began to investigate why this might have happened, and in 1942, 'nitrogen mustard' was used in a hospital in the US to treat lymphoma patients, albeit with limited success.

Nitrogen mustard works by physically modifying the DNA in your cells - it is a class of drug called an 'alkylating agent'. Work by Cancer Research UK (then the Cancer Research Campaign) in London in the 1950s led to the development of more effective alkylating agents, chlorambucil, melphalan and busulphan. These drugs are still regarded as mainstays of therapy for myeloma, lymphoma and some leukaemias.

Another class of chemotherapy drug was discovered in the 1950s - the 'antimetabolites'. These drugs resemble natural chemicals in the body, but act to block up the proteins that normally deal with them. You can think of them as a bit like a broken key - it gets stuck in the lock and the door cannot be opened. Antimetabolites such as 6-mercaptopurine and 5-fluorouracil are still in widespread use today, often as part of combination therapy.

The platinum derivatives make up another important class of chemotherapy drug. These were first discovered in 1965, when Barnett Rosenberg in Michigan was studying whether bacteria can grow in electric fields.

In his experiments, he used platinum electrodes, because platinum does not usually react with other substances. He noticed that the bacteria stopped dividing when the electric field was turned on, and assumed that this was because the electric field had stopped them dividing. However, when he turned the field off, rather than starting to divide again, the bacteria did NOT resume cell division. This meant that something else had caused them to stop dividing. After much further work, he discovered that the platinum electrode had unexpectedly reacted with the liquid the bacteria were growing in, to form a highly toxic compound.

Many years later, thanks largely to pioneering work by Cancer Research UK's Tom Connors, the first platinum derivative, cisplatin, was approved for use in cancer patients. By 1977, cisplatin, in combination with other drugs, had revolutionised the treatment of testicular cancer, and significantly improved the treatment of many other cancers.

Different classes of chemotherapy drugs work by interfering with different stages of cell division. To take advantage of this, doctors often prescribe them in combination (' combination therapy'), so that they are more effective.

Sometimes a patient can be treated with several different drugs. A huge number of  clinical trials are carried out even now to test new combinations of drugs in different sequences. Cancer Research UK is heavily involved with this type of research.

In some ways, chemotherapy is rather like taking a sledgehammer to crack a hazelnut. The drugs will affect normal body tissues as well as cancer cells, and it is this that causes the side effects. Cancer Research UK is committed to producing a new generation of more specific, better-targeted cancer therapies, to improve the quality of life of cancer patients and to minimise the risks from their treatment.

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