ABOUT CANCERCancer in medicine, common term for neoplasms, or tumors, that are malignant. Like benign tumors, malignant tumors do not respond to body mechanisms that limit cell growth. Unlike benign tumors, malignant tumors consist of undifferentiated, or unspecialized, cells that show an atypical cell structure and do not function like the normal cells from the organ from which they derive. Cancer cells, unlike normal cells, lack contact inhibition; cancer cells growing in laboratory tissue culture do not stop growing when they touch each other on a glass or other solid surface but grow in masses several layers deep.
Loss of contact inhibition accounts for two other characteristics of cancer cells: invasiveness of surrounding tissues, and metastasis, or spreading via the lymph system or blood to other tissues and organs. Whereas normal cells have a limited lifespan controlled by the telomere gene, which signals the end of the cell line, cancer cells contain telomerase, an enzyme that alters the telomere gene and allows the cell to continue to divide. Cancer tissue, growing without limits, competes with normal tissue for nutrients, eventually killing normal cells by nutritional deprivation. Cancerous tissue can also cause secondary effects, in which the expanding malignant growth puts pressure on surrounding tissue or organs or the cancer cells metastasize and invade other organs.
Virtually all organs and tissues are susceptible to cancer. Cancers are usually named for their site of origin. Cancer cells that spread to other organs are similar to those of the original tumor, therefore these secondary (metastatic) cancers are still named for their primary site even though they may have invaded a different organ. For example, lung cancer that has spread to the brain is called metastatic lung cancer, rather than brain cancer. Carcinoma in situ refers to a cancer that has not spread. (See neoplasm for more on cancer nomenclature.)
Cancer is the second leading cause of death in the United States. Lung cancer is the leading cause of cancer death in adults; leukemia is the most common cancer in children. Other common types of cancer include breast cancer (in women), prostate cancer (in men), and colon cancer (see also Hodgkin's disease ). The incidence of particular cancers varies around the world and sometimes according to ethnic group. For instance, African Americans have comparatively higher cancer rates and cancer mortality rates. It is unclear whether this is due to differences in exposure or to biological susceptibility. The number of diagnosed cases of cancer rose steadily in the United States for decades, but in 1998 it was announced that the number of new cases had begun to decline.
Causes of Cancer
Cancer results from mutations of certain genes that allow the cells to begin their uncontrolled growth. These mutations are either inherited or acquired. Acquired mutations are caused by repeated insults from triggers (e.g., cigarette smoke or ultraviolet rays) referred to as carcinogens. There is usually a latency period of years or decades between exposure to a carcinogen and the appearance of cancer. This, combined with the individual nature of susceptibility to cancer, makes it very difficult to establish a cause for many cancers.
The most significant avoidable carcinogens are the chemical components of tobacco smoke (see smoking ). Dietary components, like excessive consumption of alcohol or of foods high in fat and low in fiber rather than fruits and vegetables that contain antioxidants and necessary micronutrients, have also been linked with various cancers. Some cancers may be triggered by hormone imbalances. For example, some daughters of mothers who had been given DES (diethylstilbestrol) during pregnancy to prevent miscarriage developed vaginal adenocarcinomas as young women. Aflatoxins are natural mold byproducts that can cause cancer of the liver.
Certain carcinogens present occupational hazards. For example, in the asbestos industry, workers have a high probability of developing lung and colon cancer or a particularly virulent cancer of the mesothelium (the lining of the chest and abdomen). Benzene and vinyl chloride are other known industrial carcinogens.
X rays and radioactive elements are also carcinogenic; the high incidence of leukemia and other cancers in Japanese survivors of the atomic bombing of Hiroshima and Nagasaki and the increased incidence of thyroid cancer after the Chernobyl nuclear disaster give evidence of this. Exposure to the ultraviolet radiation of sunlight is the leading cause of skin cancer .
Many other substances have been identified as carcinogenic to a greater or lesser extent, including chemicals in pesticides that leave residues on foods. The Delaney clause, an amendment (1958) to the U.S. Food, Drug, and Cosmetic Act that prohibits even minuscule amounts of carcinogens in the food supply, has provided the impetus for the investigation of many such chemicals but has also been a source of controversy between industry and environmentalists.
In the early 20th cent., the American virologist Peyton Rous showed that certain sarcomas affecting fowl could be transmitted by injection of an agent invisible under the microscope and later indentified as an RNA-containing virus. Other research uncovered oncogenic, or tumor-causing, viruses, first in experimental animals and then in humans. The Epstein-Barr virus , a member of the herpesvirus group, has been linked with a number of human cancers, including the lymphomas that often occur in immunosuppressed people, such as people with AIDS . Several human papillomaviruses (HPV) have also been shown to initiate cancers. For example, some types of HPV cause genital warts known as condylomata acuminata, which can lead to invasive cancer of the cervix, vulva, vagina, or penis, and another human papillomavirus has been associated with some forms of Kaposi's sarcoma . In addition, hepatitis B has been shown to increase the risk of liver cancer. Bacteria have also been associated with cancer. For example, the Helicobacter pylori bacterium that causes many ulcers is also associated with an increased risk of stomach cancer.
Cancer Susceptibility
Risk to humans from carcinogens depends upon the dose and a person's biologic susceptibility. Factors influencing a person's biological susceptibility to cancer include age, sex, immune status, nutritional status, genetics, and ethnicity. Only 5% of all cancers in the United States are thought to be explained by inherited genetic mutations. Known genes associated with hereditary cancer include the aberrant BRCA1 and BRCA2 genes that increase breast cancer risk and the HNPCC gene that is linked with colon cancer. In hereditary forms, it is often the normal gene of the allele that is injured or destroyed, leaving the abnormal inherited gene in control. Nonhereditary cancers sometimes involve the same gene mutations that hereditary forms have.
Tumor Development
Most bodily insults by carcinogens come to nothing because DNA has built-in repair mechanisms, but repeated insults can eventually result in mutations or altered gene expression in key genes called oncogenes and tumor-suppressor genes. Oncogenes produce growth factors, substances that signal a cell to grow and divide into daughter cells; tumor-suppressor genes (such as the p16, p53, and BRCA1 genes) normally produce a negative growth factor that tells a cell when to stop dividing. The abnormally inactivated tumor-suppressor gene or the abnormally activated oncogene is inherited by each of the cell's daughter cells, and a tumor develops. In many cases tumors remain small and in one place ( in situ ) for years, but some develop their own blood vessels (a process known as angiogenesis) and begin to grow and spread.
Symptoms
The classic symptoms of cancer are rapid weight loss; a change in a wart or mole; a sore that does not heal; difficulty swallowing; chronic hoarseness, blood in phlegm, urine, or stool (a consequence of angiogenesis); chronic abdominal pain; a change in size or shape of the testes; a change in bowel habits; a lump in the breast; and unusual vaginal bleeding. Many of these and other symptoms are often nonspecific, e.g., weakness, loss of appetite, and weight loss, and thus are not obvious in the early stages. Sometimes the side effects of tumor growth are more severe than the actual effects of the malignancy; for example, some tumors secrete materials such as serotonin and histamine that can cause drastic vascular changes. Conversely, cancers that destroy tissue may also have serious effects, e.g., malignant destruction of bone tissue may raise the blood level of calcium.
Prevention and Detection
As more has been learned about cancer, emphasis on prevention and early detection has increased. Cessation of smoking and other tobacco use is the most important controllable means of prevention; smoking causes about 30% of the cancer deaths in the United States. A diet low in fat and high in fiber, including a variety of fruits and vegetables (especially those high in antioxidants), is also recommended. Effective protection against the rays of the sun is recommended to avoid skin cancer. Another preventive approach is vaccination against cancer-causing viruses, such as the hepatitis B virus.
Cancers caught early, before metastasis, have the best cure rates. A number of screening tools are now available to allow early detection and treatment. Among these are monthly breast self-examinations and regular mammography and Pap tests for women, regular self-examination of the testes for young men, and, for older men, regular examination of the prostate gland with blood tests for prostate-specific antigen (PSA) tumor marker (a substance in the body that heralds an increased cancer risk). Sigmoidoscopy plus physical examination and laboratory tests for carcinoembryonic antigen (CEA) are recommended for detection of colon cancer. Self-examination of the skin is important for the early detection of skin cancers. Suspicion of a tumor may be confirmed by X-ray study, endoscopy (see endoscope ), blood tests for various tumor markers, and biopsy from which the cells are examined by a pathologist for malignancy.
Treatment
Developments in the treatment of cancer have led to greatly improved
survival and quality of life for cancer patients in the past three decades. Traditionally, cancer has been treated by surgery, chemotherapy, and radiation therapy. In recent years immunotherapy has been added to that list. New drugs and techniques are constantly being researched and developed, such as antiangiogenic agents (e.g., angiostatin and endostatin), genetically engineered monoclonal antibodies , retinoid agents, and vaccine agents (stimulating the immune system).
For most kinds of cancer, surgery remains the primary treatment. It is most effective if the cancer is caught while still localized. Some cancers that spread to the lymph system are sometimes treated by extensive surgical removal of tissue, but the trend is toward more conservative procedures (see mastectomy ). Cryosurgery, the use of extreme cold, and electrodessication, the use of extreme heat, are also being used to kill cancerous tissue and the surrounding blood supply. If the cancer has metastasized, surgery is often replaced by or followed by radiation therapy (which is a localized therapy) and chemotherapy (which is a system-wide therapy).
For some cancers, radiation therapy—either from an external beam or from implanted radioactive pellets—is the primary treatment. The usual forms are X rays and gamma rays. Use of radioactive elements specific for particular target organs, such as radioactive iodine specific for the thyroid gland, is effective in treating malignancies of those organs.
Cytotoxic chemotherapy is used as a primary treatment for some cancers, such as lymphomas and leukemias or as an addition to surgery or radiation therapy. Cytotoxic drugs (drugs that are toxic to cells) are aimed at rapidly proliferating cells and interfere with nucleic acid and protein synthesis in the cancer cell, but they are often toxic to normal rapidly proliferating cells, such as bone marrow and hair cells. Often a combination of cytotoxic drugs is used. Drugs that reduce side effects may be added to the treatment, such as antinausea agents.
Hormonal chemotherapy is based upon the fact that the growth of some malignant tumors (specifically those of the reproductive organs) is influenced by reproductive hormones. Tamoxifen is a naturally occurring estrogen inhibitor used to prevent breast cancer recurrences. Flutamide is sometimes used in prostate cancer to inhibit androgen uptake. Sex-hormone related drugs such as DES and tamoxifen, which may be carcinogenic under some conditions, have proven to be protective under others.
More specifically targeted drug therapies have begun to be explored as a better understanding of the molecular biology of individual cancers has been developed. Such drugs are designed to kill only cancer cells while having fewer side effects. Gleevec (STI-571), which is used to treat chronic myelogenous leukemia and some other cancers, inhibits certain kinase receptors that become hyperactive in cancer cells, resulting in the cells' rapid reproduction.
Immunotherapy (sometimes called biological therapy) uses substances that help the body mobilize its immune defenses. Some attack the tumor itself, while others bolster the body's ability to withstand conventional chemotherapy treatment. Other new or experimental therapies include drugs that inhibit angiogenesis and photodynamic therapy, in which a patient is given a drug to make the tumor light-sensitive, after which the tumor is exposed to bright laser light. The best choice of treatment will increasingly be influenced by the growing field of molecular pathology, in which characteristics of individual cancers (e.g., virulence or resistance to a particular treatment) can be revealed by analysis of their genetic characteristics rather than by the microscope.
Besides treatment of the cancer itself, progress has been made in the management of the chronic pain that often accompanies cancer and in the education of patients and physicians in such techniques as biofeedback, acupuncture, and meditation and the appropriate use of narcotics and other medications. Because of improvements in early detection and treatment, many more people are now living with cancer. Over half of all people with cancer now survive for five or more years.
Loss of contact inhibition accounts for two other characteristics of cancer cells: invasiveness of surrounding tissues, and metastasis, or spreading via the lymph system or blood to other tissues and organs. Whereas normal cells have a limited lifespan controlled by the telomere gene, which signals the end of the cell line, cancer cells contain telomerase, an enzyme that alters the telomere gene and allows the cell to continue to divide. Cancer tissue, growing without limits, competes with normal tissue for nutrients, eventually killing normal cells by nutritional deprivation. Cancerous tissue can also cause secondary effects, in which the expanding malignant growth puts pressure on surrounding tissue or organs or the cancer cells metastasize and invade other organs.
Virtually all organs and tissues are susceptible to cancer. Cancers are usually named for their site of origin. Cancer cells that spread to other organs are similar to those of the original tumor, therefore these secondary (metastatic) cancers are still named for their primary site even though they may have invaded a different organ. For example, lung cancer that has spread to the brain is called metastatic lung cancer, rather than brain cancer. Carcinoma in situ refers to a cancer that has not spread. (See neoplasm for more on cancer nomenclature.)Cancer is the second leading cause of death in the United States. Lung cancer is the leading cause of cancer death in adults; leukemia is the most common cancer in children. Other common types of cancer include breast cancer (in women), prostate cancer (in men), and colon cancer (see also Hodgkin's disease ). The incidence of particular cancers varies around the world and sometimes according to ethnic group. For instance, African Americans have comparatively higher cancer rates and cancer mortality rates. It is unclear whether this is due to differences in exposure or to biological susceptibility. The number of diagnosed cases of cancer rose steadily in the United States for decades, but in 1998 it was announced that the number of new cases had begun to decline.
Causes of Cancer
Cancer results from mutations of certain genes that allow the cells to begin their uncontrolled growth. These mutations are either inherited or acquired. Acquired mutations are caused by repeated insults from triggers (e.g., cigarette smoke or ultraviolet rays) referred to as carcinogens. There is usually a latency period of years or decades between exposure to a carcinogen and the appearance of cancer. This, combined with the individual nature of susceptibility to cancer, makes it very difficult to establish a cause for many cancers.
The most significant avoidable carcinogens are the chemical components of tobacco smoke (see smoking ). Dietary components, like excessive consumption of alcohol or of foods high in fat and low in fiber rather than fruits and vegetables that contain antioxidants and necessary micronutrients, have also been linked with various cancers. Some cancers may be triggered by hormone imbalances. For example, some daughters of mothers who had been given DES (diethylstilbestrol) during pregnancy to prevent miscarriage developed vaginal adenocarcinomas as young women. Aflatoxins are natural mold byproducts that can cause cancer of the liver.
Certain carcinogens present occupational hazards. For example, in the asbestos industry, workers have a high probability of developing lung and colon cancer or a particularly virulent cancer of the mesothelium (the lining of the chest and abdomen). Benzene and vinyl chloride are other known industrial carcinogens.
X rays and radioactive elements are also carcinogenic; the high incidence of leukemia and other cancers in Japanese survivors of the atomic bombing of Hiroshima and Nagasaki and the increased incidence of thyroid cancer after the Chernobyl nuclear disaster give evidence of this. Exposure to the ultraviolet radiation of sunlight is the leading cause of skin cancer .
Many other substances have been identified as carcinogenic to a greater or lesser extent, including chemicals in pesticides that leave residues on foods. The Delaney clause, an amendment (1958) to the U.S. Food, Drug, and Cosmetic Act that prohibits even minuscule amounts of carcinogens in the food supply, has provided the impetus for the investigation of many such chemicals but has also been a source of controversy between industry and environmentalists.
In the early 20th cent., the American virologist Peyton Rous showed that certain sarcomas affecting fowl could be transmitted by injection of an agent invisible under the microscope and later indentified as an RNA-containing virus. Other research uncovered oncogenic, or tumor-causing, viruses, first in experimental animals and then in humans. The Epstein-Barr virus , a member of the herpesvirus group, has been linked with a number of human cancers, including the lymphomas that often occur in immunosuppressed people, such as people with AIDS . Several human papillomaviruses (HPV) have also been shown to initiate cancers. For example, some types of HPV cause genital warts known as condylomata acuminata, which can lead to invasive cancer of the cervix, vulva, vagina, or penis, and another human papillomavirus has been associated with some forms of Kaposi's sarcoma . In addition, hepatitis B has been shown to increase the risk of liver cancer. Bacteria have also been associated with cancer. For example, the Helicobacter pylori bacterium that causes many ulcers is also associated with an increased risk of stomach cancer.Cancer Susceptibility
Risk to humans from carcinogens depends upon the dose and a person's biologic susceptibility. Factors influencing a person's biological susceptibility to cancer include age, sex, immune status, nutritional status, genetics, and ethnicity. Only 5% of all cancers in the United States are thought to be explained by inherited genetic mutations. Known genes associated with hereditary cancer include the aberrant BRCA1 and BRCA2 genes that increase breast cancer risk and the HNPCC gene that is linked with colon cancer. In hereditary forms, it is often the normal gene of the allele that is injured or destroyed, leaving the abnormal inherited gene in control. Nonhereditary cancers sometimes involve the same gene mutations that hereditary forms have.
Tumor Development
Most bodily insults by carcinogens come to nothing because DNA has built-in repair mechanisms, but repeated insults can eventually result in mutations or altered gene expression in key genes called oncogenes and tumor-suppressor genes. Oncogenes produce growth factors, substances that signal a cell to grow and divide into daughter cells; tumor-suppressor genes (such as the p16, p53, and BRCA1 genes) normally produce a negative growth factor that tells a cell when to stop dividing. The abnormally inactivated tumor-suppressor gene or the abnormally activated oncogene is inherited by each of the cell's daughter cells, and a tumor develops. In many cases tumors remain small and in one place ( in situ ) for years, but some develop their own blood vessels (a process known as angiogenesis) and begin to grow and spread.
Symptoms
The classic symptoms of cancer are rapid weight loss; a change in a wart or mole; a sore that does not heal; difficulty swallowing; chronic hoarseness, blood in phlegm, urine, or stool (a consequence of angiogenesis); chronic abdominal pain; a change in size or shape of the testes; a change in bowel habits; a lump in the breast; and unusual vaginal bleeding. Many of these and other symptoms are often nonspecific, e.g., weakness, loss of appetite, and weight loss, and thus are not obvious in the early stages. Sometimes the side effects of tumor growth are more severe than the actual effects of the malignancy; for example, some tumors secrete materials such as serotonin and histamine that can cause drastic vascular changes. Conversely, cancers that destroy tissue may also have serious effects, e.g., malignant destruction of bone tissue may raise the blood level of calcium.
Prevention and Detection
As more has been learned about cancer, emphasis on prevention and early detection has increased. Cessation of smoking and other tobacco use is the most important controllable means of prevention; smoking causes about 30% of the cancer deaths in the United States. A diet low in fat and high in fiber, including a variety of fruits and vegetables (especially those high in antioxidants), is also recommended. Effective protection against the rays of the sun is recommended to avoid skin cancer. Another preventive approach is vaccination against cancer-causing viruses, such as the hepatitis B virus.
Cancers caught early, before metastasis, have the best cure rates. A number of screening tools are now available to allow early detection and treatment. Among these are monthly breast self-examinations and regular mammography and Pap tests for women, regular self-examination of the testes for young men, and, for older men, regular examination of the prostate gland with blood tests for prostate-specific antigen (PSA) tumor marker (a substance in the body that heralds an increased cancer risk). Sigmoidoscopy plus physical examination and laboratory tests for carcinoembryonic antigen (CEA) are recommended for detection of colon cancer. Self-examination of the skin is important for the early detection of skin cancers. Suspicion of a tumor may be confirmed by X-ray study, endoscopy (see endoscope ), blood tests for various tumor markers, and biopsy from which the cells are examined by a pathologist for malignancy.
Treatment
Developments in the treatment of cancer have led to greatly improved
survival and quality of life for cancer patients in the past three decades. Traditionally, cancer has been treated by surgery, chemotherapy, and radiation therapy. In recent years immunotherapy has been added to that list. New drugs and techniques are constantly being researched and developed, such as antiangiogenic agents (e.g., angiostatin and endostatin), genetically engineered monoclonal antibodies , retinoid agents, and vaccine agents (stimulating the immune system).For most kinds of cancer, surgery remains the primary treatment. It is most effective if the cancer is caught while still localized. Some cancers that spread to the lymph system are sometimes treated by extensive surgical removal of tissue, but the trend is toward more conservative procedures (see mastectomy ). Cryosurgery, the use of extreme cold, and electrodessication, the use of extreme heat, are also being used to kill cancerous tissue and the surrounding blood supply. If the cancer has metastasized, surgery is often replaced by or followed by radiation therapy (which is a localized therapy) and chemotherapy (which is a system-wide therapy).
For some cancers, radiation therapy—either from an external beam or from implanted radioactive pellets—is the primary treatment. The usual forms are X rays and gamma rays. Use of radioactive elements specific for particular target organs, such as radioactive iodine specific for the thyroid gland, is effective in treating malignancies of those organs.
Cytotoxic chemotherapy is used as a primary treatment for some cancers, such as lymphomas and leukemias or as an addition to surgery or radiation therapy. Cytotoxic drugs (drugs that are toxic to cells) are aimed at rapidly proliferating cells and interfere with nucleic acid and protein synthesis in the cancer cell, but they are often toxic to normal rapidly proliferating cells, such as bone marrow and hair cells. Often a combination of cytotoxic drugs is used. Drugs that reduce side effects may be added to the treatment, such as antinausea agents.
Hormonal chemotherapy is based upon the fact that the growth of some malignant tumors (specifically those of the reproductive organs) is influenced by reproductive hormones. Tamoxifen is a naturally occurring estrogen inhibitor used to prevent breast cancer recurrences. Flutamide is sometimes used in prostate cancer to inhibit androgen uptake. Sex-hormone related drugs such as DES and tamoxifen, which may be carcinogenic under some conditions, have proven to be protective under others.
More specifically targeted drug therapies have begun to be explored as a better understanding of the molecular biology of individual cancers has been developed. Such drugs are designed to kill only cancer cells while having fewer side effects. Gleevec (STI-571), which is used to treat chronic myelogenous leukemia and some other cancers, inhibits certain kinase receptors that become hyperactive in cancer cells, resulting in the cells' rapid reproduction.
Immunotherapy (sometimes called biological therapy) uses substances that help the body mobilize its immune defenses. Some attack the tumor itself, while others bolster the body's ability to withstand conventional chemotherapy treatment. Other new or experimental therapies include drugs that inhibit angiogenesis and photodynamic therapy, in which a patient is given a drug to make the tumor light-sensitive, after which the tumor is exposed to bright laser light. The best choice of treatment will increasingly be influenced by the growing field of molecular pathology, in which characteristics of individual cancers (e.g., virulence or resistance to a particular treatment) can be revealed by analysis of their genetic characteristics rather than by the microscope.Besides treatment of the cancer itself, progress has been made in the management of the chronic pain that often accompanies cancer and in the education of patients and physicians in such techniques as biofeedback, acupuncture, and meditation and the appropriate use of narcotics and other medications. Because of improvements in early detection and treatment, many more people are now living with cancer. Over half of all people with cancer now survive for five or more years.
