GENERAL DEFINITION OF CANCER

Although cancer is often referred to as a single condition, it actually consists of more than 100 different diseases, all characterized by the uncontrolled growth and spread of abnormal cells. Cancer can arise in many sites and behaves differently depending on its organ of origin. Thus, breast cancer has different characteristics than lung cancer, and breast cancer that spreads to the lungs should not be confused with lung cancer. Even in the lungs, breast cancer continues to behave like breast cancer and, under the microscope, continues to look like breast cancer.

  THE CELL BIOLOGY OF CANCER
Each of the organs in the body, such as the lung, breast, colon, and brain, consists of specialized cells that carry out the organ's functions, such as transport of oxygen, digestion of nutrients, excretion of waste materials, locomotion, reproduction, and thinking. For the proper performance of each organ, worn out or injured cells must be replaced, and particular types of cells must increase in response to environmental changes. For example, the bone marrow is able to increase its production of oxygen-carrying red blood cells seven-fold or greater in response to bleeding or high altitude, and certain white blood cells are produced more rapidly during infections. Similarly, the liver or endocrine organs frequently respond to injury by regenerating damaged cells.

Regulation of cell reproduction is complex and varied for each type of tissue. In general, cells are of three types.

Stem Cells—capable of reproduction through multiple divisions.
Committed Cells—divide only a defined number of times, and are limited in capacity for self-renewal.
Specialized Cells—carry out organ function and are incapable of cell division.

An internal feedback system controls cell division by balancing the number of old and dying cells against the progeny of the stem cells. Cells divide until the body or organ reaches a specific—usually adult—size or stage and then cease dividing unless a specific need arises.

Stem cells divide most rapidly in organs where cells are continually shed and replaced such as the skin, bone marrow (which produces blood), and cells lining the intestinal tract. Muscles and bone grow less rapidly (muscles increasing in size in response to use) while bone repairs itself in response to fracture. In contrast, adult nerves, which are composed mainly of specialized cells, hardly grow at all and have only a limited capacity to repair damage from injury or disease.

The presence of feedback control systems and the ability of cells to respond to signals to divide or die distinguish the behavior of normal tissues from cancer cells. Unlike normal cells, cancer cells ignore signals to stop dividing, to specialize, or to die and be shed.

All cancers lose a balance between the number of new cells produced and the number of mature cells that die. In normal adult organs, equal numbers of cells are produced and die each day, and only growing fetuses, children, and regenerating injured tissue produce more new cells than die.

Genes that control the genetics and heredity of each cell are strung like beads on a necklace along the cell's DNA (deoxyribonucleic acid) in the cell nucleus (see figure 17.1). In a benign or malignant tumor, several of the genes regulating these processes are abnormal (mutated). Abnormal genes may be inherited or damaged by carcinogens, viruses, errors in cell division, or as yet unknown factors.

As cancerous malignant tumors develop, additional genes are damaged, leading to:

1. Production of more cells or reduction in normal cell death rate
2. Shedding into the bloodstream of cells capable of spreading and growing in a new location (metastasis)
3. Capacity of metastatic tumor cells to attract the capillary development to feed their growth. Lack of a blood supply would otherwise limit tumor cell growth to a small size that would be of no danger.

Cancer cells do not necessarily grow faster than normal cells, but they persist longer or divide more times during their lifetime. Consequently, cancer cells accumulate, competing with normal, healthy tissue for nutrients, and encroaching on the space and territory of other cells. Many cancers, such as prostate cancer, grow slowly and may be present for many years before causing symptoms. Prostate cancer is rarely evident in men in their 40s, but by age 85 or 90, most men have some cancer cells in their prostate, although this condition is usually localized and not a serious medical problem. Cancer in children, on the other hand, tends to grow more quickly than in adults because children's body tissues generally grow rapidly.

  HORMONE-PRODUCING TUMORS
A number of cancers affect the endocrine system, either by directly influencing a specific endocrine gland or by producing an uncontrolled supply of hormones. Since hormonal imbalances can affect virtually every organ and body function, hormone-producing tumors can cause a wide range of symptoms.

• Certain lung cancers can provoke the overproduction of antidiuretic hormone, causing body fluids to accumulate and resulting in severe imbalances of electrolytes (blood salts).
• Metastatic breast cancer, multiple myeloma, bone cancers, and other advanced or metastatic cancers frequently cause hypercalcemia (high calcium levels in the blood) as a result of tumor production of prostaglandins, substances similar to the hormones normally secreted by the parathyroid, and a variety of other hormones (see "Cancer Emergency Symptoms," later in this chapter).
• Tumors of the adrenal cortex may produce excess corticosteroid hormones (Cushing's syndrome).
• Rare tumors of the male or female gonads may produce inappropriate amounts of virilizing or feminizing hormones.
• Tumors that are derived from endocrine tissue such as pancreatic islet cells may produce excessive amounts of insulin or related hormones.

Some cancers disrupt the body's functions with the production of hormonelike substances. For example, the loss of taste and appetite in many people with advanced cancers, resulting in severe wasting of both fatty and lean tissue (cachexia), is due in part to a substance called TNF (tumor necrosis factor).

Cancers of the breast and prostate frequently possess hormone receptors that allow their growth to be stimulated or retarded by specific hormones. For these cancers, hormone treatment may relieve symptoms. Consequently, men with advanced prostate cancer may be administered estrogen and women with advanced breast cancer may be given estrogen or tamoxifen, a drug that blocks estrogen production and uptake. Studies have shown that tamoxifen treatment may decrease the risk of cancer recurrence even for women whose tumors have negative estrogen receptor tests.