Chemotherapy: 101.

Chemotherapy is the use of chemicals to destroy cancer cells and works by

interfering with the cancer cell's ability to grow. Radiation therapy and surgery
are also employed; both of which may be used in conjunction with
chemotherapy. What makes chemotherapy very effective, is that it has the
ability to treat widespread (metastatic) cancer, that is in more than one
location in your body. There are many different types of drugs that qualify as
chemotherapy agents, and the drug that is chosen depends on the type of
cancer. Antineoplastic drugs are classified into five major categories based on
the way the drugs affect cell chemistry, and which stage of the cells life cycle
the drugs effect.

Cell Cycles.

Each cell goes through a four phase cycle in order to replicate itself. The first
phase called G1 and it is when the cell prepares to replicate its chromosomes.
The second stage is called S, and in this phase DNA synthesis occurs and the
DNA is duplicated. The next phase is the G2 phase, when the RNA and protein
duplicate. The final stage is the M stage, which is the stage of actual cell
division. In this final stage, the duplicated DNA and RNA split and move to
separate ends of the cell, and the cell actually divides into two identical,
functional cells.

Depending on the drug chosen, chemotherapy will affect malignant cells in one
of three ways:

Damage the DNA of the cancer cells so they can no longer reproduce.
This is done by altering the DNA structure in the nucleus of the cell
preventing replication.
During the S phase of cell life, inhibit the synthesis of new DNA strands so
that no cell replication is possible. This occurs when the drugs block the
formation of nucleotides that are necessary for new DNA to be created.
Stop the mitotic processes of the cell so that the cancer cell cannot
divide into two cells. The formation of mitotic spindles is necessary to move
 the original DNA and the replicated DNA to opposite sides of the cell so
the cell can divide into two cells.

Current chemotherapy drugs will act in one of these ways to achieve the
ultimate goal of killing the cancer cells in the body.

Image Courtesy of Fotolia

The drugs used in chemotherapy are divided into five broad categories. They
are placed in these categories depending on their role in the destruction of
cancer cells. More specifically, the drugs are classified into a specific category
depending on what part of the cell cycle the drug interrupts. These categories
are Alkylating Agents, Nitrosoureas, Antimetabolites, Antitumor Antibiotics, Plant
Alkaloids, and Steroid Hormones.

ALKYLATING AGENTS are drugs that work by directly attacking the DNA of a cell.
These drugs can work at any time of the cell cycle, but are most effective during
DNA synthesis. They are used to treat Hodgkin's disease, lymphomas, chronic
leukemias, and certain carcinomas of the lung, breast, prostrate, and ovary.
Alkylating agents are administered either orally or intravenously. Examples of
drugs in this category are Cyclophosphamide and Mechlorethamine, Cisplatin
(Platinol).

Because these drugs damage DNA, they can cause long term-damage to the
bone marrow. In rare cases, this can lead to acute leukemia. The risk of
leukemia from alkylating agents is dose-dependent, meaning that the risk is
small with lower doses, but goes up as the total amount of the drug used gets
higher. The risk of leukemia after getting alkylating agents is highest about 5 to
10 years after treatment.

Alkylating agents are divided into different classes, including:

Nitrogen mustards: such as mechlorethamine (nitrogen mustard), chlorambucil,

cyclosphosphamide, ifosfamied and melphalan

Nitrosoureas: are similar to alkylating agents, and work by inhibiting the changes
necessary for DNA repair. A very important feature of this class of drugs is that
they can cross the blood-brain barrier which makes them very useful for treating
brain tumors. They can also be used to treat lymphomas and melanomas.
Nitrosoureas are administered either orally or intravenously. Examples of drugs in
this category are Carmustine and Lomustine.

Alkyl sulfonates: busulfan

Triazines: dacarbazine and temozolomide

Ethylenimines: thiotepa and altretamine

The platinum drugs (such as cistaplin, carboplatin and oxalaplatin) are

sometimes grouped with alkylating agents because they kill cells in a similar
way. These drugs are less likely than the alkylating agents to cause leukemia
later.
ANTIMETABOLITES block cell growth by interfering with DNA synthesis. These drugs
work by mimicking a substance involved in DNA synthesis, inhibiting production
of an acid necessary for DNA to be synthesized. These drugs affect the "S" phase
of the cell cycle. They are administered either orally or intravenously. Examples
of these drugs are 6-mercaptopurine, capecitabine, floxuridine, methotrexate 5-
fluorouracil and gemcitabine.

ANTITUMOR ANTIBIOTICS. These drugs are not like the antibiotics used to treat
infections. They work by binding with DNA (altering DNA inside cancer cells to
keep them from growing and multiplying) to prevent RNA synthesis. These also
prevent cell growth by preventing DNA replication. Antitumor antibiotics prevent
the DNA from reattaching itself together which causes the cell to die.
Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in
DNA replication. These drugs work in all phases of the cell cycle. They are
widely used for a variety of cancers. Antitumor antibiotic drugs are administered
intravenously. Some examples of this category are Doxorubicin and Epirubicin.

Anti-tumor antibiotics that are not anthracyclines include:

Actinomycin-D, Bleomycin, Mitomycin-C and Mitoxantrone (also acts as a

topoisonmerase II inhibitor)

A major concern when giving these drugs is that they can permanently
damage the heart if given in high doses. For this reason, lifetime dose limits are
often placed on these drugs.

PLANT(VINCA) ALKALOIDS. Mitotic inhibitors are often plant alkaloids and other
compounds derived from natural products. They work by stopping mitosis in the
M phase of the cell cycle but can damage cells in all phases by keeping
enzymes from making proteins needed for cell reproduction. During
metaphase, mitotic spindles hold the two sets of DNA the cell needs to divide.
The spindles are formed using a protein called tubulin. Plant alkaloids bind to
tubulin, which prevents the formation of mitotic spindles. Without mitotic
spindles, the cell cannot divide. Plant alkaloids are administered intravenously.
Some examples of this category are Paclitaxel, Docetaxel, Vincristine and
Vinblastine.

STEROID HORMONES. These drugs modify the growth of hormone dependant

cancers. Corticosteroids, often simply called steroids, are natural hormones and
hormone-like drugs that are useful in the treatment of many types of cancer, as
well as other illnesses.They induce a change in the three dimensional shape of
the receptor on a cell preventing the cell's binding to the needed estrogen
response element on the DNA. These drugs are most commonly used in treating
breast cancer. The hormones are administered orally. Examples of
corticosteroids include: Prednisone, Methylprednisone and Dexamethasone.

NOTE: Some chemotherapy drugs act in slightly different ways and do not fit
well into any of the other categories. Examples include drugs lke L-
asparaginase, which is an enzyme, and the proteasome inhibitor bortezomib.