Chemotherapy: a Great Medical Innovation of the 20th Century

Cancer is a disease with a devastating impact in terms of mortality as well as physical and
psychosocial morbidity. It is one of the highest leading causes of death. Chemotherapy being a very
popular treatment in the medical society that has become an effective way to treat cancer patients, was
discovered in the early 20th century when military doctors noticed deaths of soldiers due to exposure
to mustard gas which damaged their rapidly growing white blood cells. As cancer is characterised by
an uncontrolled growth of abnormal cells in the body, doctors reasoned that the nitrogen mustard
might have a similar effect on cancer. Therefore, in 1942, nitrogen mustard was used and given by
vein to several lymphoma patients. Albeit with limited success, their improvement was remarkable.
Mustine was the first chemotherapy drug to be developed from the mustard gas line of research.
Traditional chemotherapy drugs act by killing cells that divide rapidly, whereas most normal
cells in the body do not. However, some cells such as cells in the bone marrow, immune cells,
digestive track, and hair follicles cells also divide rapidly and are harmed during chemotherapy. As
results, chemotherapy drugs often have unpleasant side effects such as nausea, hair loss and vomiting.
Chemotherapy may use one drug at a time which is known as single-agent chemotherapy or several
drugs at once called combination chemotherapy. These drugs can either be delivered directly to
specific cancer sites or they can be transported by the blood stream to attack cancer cells throughout
the body, most do not cross the blood-brain barrier and therefore cannot reach the central nervous
system.
Chemotherapy drugs have been classified into different groups based on their ability to
destroy cancer cells. The first classification is known as alkylating agents. Alkylating agents are the
oldest group of chemotherapeutics in use today. These agents directly damage DNA to prevent the
cancer cells from reproducing. Because these drugs damage DNA, they can cause long-term damage
to the bone marrow. Nitrogen mustards are example drugs of alkylating agents. Anti-metabolites are
another classification of drugs that interfere with DNA and RNA growth. These drugs work by
substituting the normal building blocks of DNA and RNA. This doesnt allow the real purine which
contains the 2 nucleic acids adenine and guanine to become part of the DNA during the S phase of the
cell cycle. Anti-tumor antibiotics are another category of chemotherapy drugs. Anthracyclines are
anti-tumor antibiotics that interfere with enzymes involving DNA replication. This prevents mitosis.
As DNA molecules cannot duplicate itself, RNA will not be synthesised either. Mitotic inhibitors are
another type of drugs that inhibit enzymes from making proteins needed for cell reproduction.
Chromatins are attached to the mitotic spindles which are formed through the use of protein tubulin.
The drug binds itself with the protein tubulin. This prevents it to make spindles. The cell cannot
divide if it does not have mitotic spindles forming during cell division.
A major cause of failure in treatment is caused by resistance to chemotherapy drugs. There
are few causes of resistance, one of which is when cancer cells produce pumps on the surface of the
cell. These pumps move chemotherapy to move from inside of the cell to the outside. These pumps
are known as p-glycoprotein. Drugs to inhibit the synthesis or function of p-glycoprotein are still
under investigation. Another type of resistance is gene amplification. This is a process where cancer
cells produce multiple copies of a gene. The numerous gene copies overcome the effect of drugs that
destroy the genes involving replication. As most chemotherapy drugs kill cancer cells by apoptosis,
death of cell, cancer cells defect in cellular pathways of apoptosis. Defective apoptosis allows survival
of these cells making them resistant. There are enzymes in cells present which function is to repair

damaged DNA. These are also present in cancer cells. Many chemotherapy drugs work by damaging
DNA of the cancer cell which can be repaired by the enzymes. Repairing and modifying of the cancer
cell genes can overcome the DNA damage and prevent induction of apoptosis. Other chemotherapy
drugs work by binding itself to one of the proteins, such as tubulin, in the cancer cell. Mutations in
genes that produce drug target proteins can occur which will prevent the drugs to bind to the protein,
leading to resistance to these types of drugs.
Chemotherapy may not cure every cancer patient, but it is proven to be one of the most
effective treatments for cancer. Since its first discovery, more than 50 different chemotherapy drugs
have been developed for cancer treatment, each having a different way of affecting cancer cells.
Advancements in this treatment have made it popular and an easy form of treatment for an everyday
person. Researchers are currently looking for new and improved drugs that will help this growing
health problem today. Chemotherapy treatment is improving and the success rates are increasing.