POISON PILL
CANCER A disease of unregulated cell division: cells divide inappropriately and accumulate, in some instances forming a tumor.
CHEMOTHERAPY The treatment of disease, specifically cancer, by the use of chemicals.
Although taxol made a splash when it first entered the clinic, it was no overnight success story. In fact, the roots of the drug extend back more than a half-century. Before 1945, there were basically two ways to treat cancer: cut it out or zap it with radiation. These methods worked well for some cancers, but against others they were relatively powerless. Researchers were desperate for a better way.
CELL DIVISION The process by which a cell reproduces itself; cell division is important for normal growth, development, and repair of an organism.
Then, during World War II, medical officers stumbled upon an important find: soldiers who had been exposed to the poison known as mustard gas had severely lowered white blood cell counts. Autopsies revealed that cells in the normally rapidly dividing bone marrow had stopped dividing. Since cancer of the bone marrow resulted from uncontrolled cell division there, scientists wondered if the deadly poison might be used as a cancer treatment. To their surprise and delight, tests on patients conducted in 1942 proved that it could. Chemotherapy–the treatment of disease by chemicals–was born.
Most commonly, chemotherapeutic drugs are used to treat cancer. There are different classes of these drugs, but as researchers soon learned, most work by interfering with a fundamental part of a cell’s life: cell division.
Although we may think of our bodies as relatively fixed structures, most of our tissues are in constant flux as cells divide periodically to replace cells that have reached the end of their life span. In fact, cell division in our bodies begins long before we are even born. During embryonic development, a single fertilized egg cell divides, and its daughter cells divide again and again, eventually forming trillions of cells by the time a baby is born. As we age, our tissues continually discard old cells and generate new ones in their place. And when we cut or injure ourselves, cells in the area divide to heal the wound (INFOGRAPHIC 9.1).
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CELL CYCLE The ordered sequence of stages that a cell progresses through in order to divide during its life; stages include preparatory phases (G1, S, G2) and division phases (mitosis and cytokinesis).
Certain cells divide more frequently than others—bone marrow cells divide continuously, for example, whereas brain cells divide at a much slower rate or not at all. And cancer cells divide uncontrollably.
INTERPHASE The stage of the cell cycle in which cells spend most of their time, preparing for cell division. There are three distinct sub-phases: G1, S, and G2.
To produce new cells, cells pass through a series of stages collectively known as the cell cycle. During the cell cycle, one cell becomes two. A cell doesn’t simply split in half, however. If it did, each resulting cell would be smaller than the original, and with each division, each cell would lose half its contents. So before a cell divides, it first makes a copy of its contents so that each new cell has the same amount of organelles, DNA, and cytoplasm as the original cell. This preparatory stage of the cell cycle, known as interphase, has separate subphases: G1 phase, when the cell grows larger and begins to produce more cytoplasm and organelles; synthesis phase (S), when DNA replicates and chromosomes are therefore duplicated; and G2 phase, when the cell is ready to enter the division phases. In a cell that takes approximately 24 hours to divide, interphase takes about 22 hours to complete.
MITOSIS The segregation and separation of duplicated chromosomes during cell division.
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CYTOKINESIS The physical division of a cell into two daughter cells.
Once the cell duplicates its contents, it enters the division phases of the cell cycle: mitosis, when the chromosomes are evenly divided between the two daughter cells; and cytokinesis, when the two daughter cells physically separate. During mitosis, the duplicated chromosomes line up along the midline of the cell. Each duplicated chromosome is made up of two identical sister chromatids connected at a region called the centromere. The two sister chromatids of each replicated chromosome are then pulled apart from each other. Each chromatid will form one of two genetically identical chromosomes in a daughter cell. During cytokinesis, the enlarged cell splits into two separate cells, each containing a full complement of organelles and DNA. In this way, one parent divides into two new daughter cells, each of which is identical to the original parent cell (INFOGRAPHIC 9.2). Mitosis and cytokinesis take about 2 hours to complete in cells with a 24-hour cell cycle
SISTER CHROMATIDS The two identical DNA molecules that make up a duplicated chromosome following DNA replication.
CENTROMERE The specialized region of a chromosome where the sister chromatids are joined; critical for proper alignment and separation of sister chromatids during mitosis.
The purpose of the cell cycle is to replicate cells, creating two new daughter cells that are genetically identical to the original parent cell. The cell cycle consists of preparatory phases collectively known as interphase, as well as the division phases, mitosis and cytokinesis.
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Most of today’s chemotherapy drugs target one or more elements of the cell cycle. Some drugs interfere with cells’ ability to copy their DNA and thus to replicate. Other drugs interfere with other steps of the cell cycle, such as the ability of the cells to separate their chromosomes. Unable to complete these important steps of cell division, the cells die.