The word cancer elicits dread in everyone. Why does cancer strike some and not others?
Although once perceived as disorganized cell growth, this disease is now known to be a logical, coordinated process in which a precise sequence of tiny alterations changes a normal cell into a killer. Let’s take a closer look at what cancer really is.
When cells fail to honor normal controls of cell division and multiply excessively, an abnormal mass of proliferating cells called a neoplasm (ne′o-plazm, “new growth”) results. Neoplasms are classified as benign (“kindly”) or malignant (“bad”). A benign neoplasm is strictly a local affair. Its cells remain compacted, are often encapsulated, tend to grow slowly, and seldom kill their hosts if they are removed before they compress vital organs. In contrast, cancers are malignant neoplasms, nonencapsulated masses that grow relentlessly and may become killers. Their cells resemble immature cells, and they invade their surroundings rather than pushing them aside, as reflected in the name cancer, from the Latin word for “crab.” Whereas normal cells become fatally “homesick” and die when they lose contact with the surrounding matrix, malignant cells tend to break away from the parent mass, the primary tumor, and travel via blood or lymph to other body organs, where they survive and form secondary cancer masses. This capability for traveling to other parts of the body, called metastasis (mĕ-tas′tah-sis), probably has a lot to do with cell surface glycoproteins the cancer cells bear. For example, a carbohydrate called sialyl Lewis X binds to adhesion molecules on epithelial cells and platelets. Metastasis and invasiveness distinguish cancer cells from the cells of benign neoplasms. Cancer cells consume an exceptional amount of the body’s nutrients, leading to weight loss and tissue wasting that contribute to death.
Mechanisms of Carcinogenesis
Autopsies on individuals aged 50–70 who died of another cause have revealed that most of them (us) have microscopic (but dormant) in situ neoplasms. So what causes a normal cell to transform or change into a cancerous one? Some physical factors (radiation, mechanical trauma), certain viral infections, chronic inflammations, and many chemicals (tobacco tars, saccharine, some natural food chemicals) can act as carcinogens (cancer-causers). What these factors have in common: They all cause mutations—changes in DNA that alter the expression of certain genes. However, not all carcinogens do damage because most are eliminated by peroxisomal or lysosomal enzymes or by the immune system. Furthermore, one mutation usually isn’t enough; it takes several genetic changes to transform a normal cell into a cancerous cell.
A clue to the role of genes in cancer was provided by the discovery of oncogenes (Greek onco = tumor), or cancer-causing genes, in rapidly spreading cancers. Proto-oncogenes, benign forms of oncogenes in normal cells, were discovered later. Proto-oncogenes code for proteins that are essential for cell division, growth, and cellular adhesion, among other things. Many have fragile sites that break when exposed to carcinogens, converting them to oncogenes. Failure to code for certain proteins may lead to loss of an enzyme that controls an important metabolic process. Oncogenes, now known to number over 100, may also “switch on” dormant genes that allow cells to become invasive and metastasize.
Oncogenes have been detected in only 15–20% of human cancers, so investigators were not too surprised by the discovery of tumor suppressor genes, or antioncogenes, which suppress cancer by inactivating carcinogens, aiding DNA repair, or enhancing the immune system’s counterattack. In fact, over half of all cancers involve malfunction or loss of just two of the 15 identified tumor suppressor genes—p53 and p16. This is not surprising when you learn that p53 prompts most cells to make proteins that put the brakes on cell division in stressed cells by promoting apoptosis or cell cycle arrest. Hence, its impairment invites uncontrolled division and cancer. Furthermore, although each type of cancer is genetically distinct, human cancers appear to share a common master set of genes—an activated group of 67 genes—and almost all cancer cells have gained or lost entire chromosomes. Whatever genetic factors are at work, the “seeds” of cancer do appear to be in our own genes. Thus, cancer is an intimate enemy indeed.
The illustration depicts some of the mutations involved in colorectal cancer, one of the best-understood human cancers. As with most cancers, a metastasis develops gradually. One of the first signs is a polyp, a small benign growth consisting of apparently normal mucosa cells. As cell division continues, the growth enlarges, becoming an adenoma. As various tumor-suppressor genes are inactivated and the K-ras oncogene is mobilized, the mutations pile up and the adenoma becomes increasingly abnormal. The final consequence is colon carcinoma, a form of cancer that metastasizes quickly.
Cancer Prevalence
Almost half of all Americans develop cancer in their lifetime and a fifth of us will die of it. Cancer can arise from almost any cell type, but the most common cancers originate in the skin, lung, colon, breast, and prostate gland. Although stomach and colon cancer incidence is down, skin and lymphoid cancer rates are up.
Many cancers are preceded by observable lumps or other structural changes in tissue—for instance, leukoplakia, white patches in the mouth caused by the chronic irritation of ill-fitting dentures or heavy smoking. Although these lesions sometimes progress to cancer, in many cases they remain stable or even revert to normal if the environmental stimulus is removed.
Diagnosis and Staging
Screening procedures are vital for early detection. Examples include mammography, examining breasts or testicles for lumps, and checking fecal samples for blood. Unfortunately, most cancers are diagnosed only after symptoms have already appeared. In this case the diagnostic method is usually a biopsy: removing a tissue sample surgically and examining it microscopically for malignant cells. Increasingly, diagnosis is made by chemical or genetic analysis of the sample. Typing cancer cells by what genes are switched on or off tells clinicians which drugs to use. For example, taxol, quite successful with breast and ovarian cancer, works only against tumors with a specific genetic makeup. Medical imaging techniques (MRI, CT) can detect large tumors.
Several techniques (physical and histological examinations, lab tests, and imaging techniques) are used to determine the extent of the disease (size of the neoplasm, degree of metastasis, etc.). Then, the cancer is assigned a stage from 1 to 4 according to the probability of cure (stage 1 has the best probability, stage 4 the worst).
Cancer Treatments
Most cancers are removed surgically if possible. To destroy metastasized cells, surgery is commonly followed by radiation therapy (X irradiation and/or treatment with radioisotopes) and chemotherapy (treatment with cytotoxic drugs). Chemotherapy is beset with the problem of resistance. Some cancer cells can eject the drugs in tiny bubbles or flattened vesicles dubbed exosomes, and these cells proliferate, forming new tumors that are invulnerable to chemotherapy. Furthermore, anticancer drugs have unpleasant side effects—nausea, vomiting, hair loss—because they kill all rapidly dividing cells, including normal tissues and cells. X rays also have side effects because, in passing through the body, they destroy healthy tissue in their path as well as cancer cells.
Promising New Therapies
Traditional cancer treatments—”cut, burn, and poison”—are widely recognized as crude and painful. Promising new therapies focus on
Targeted drugs that interrupt the signaling pathways which fuel the cancer’s growth. Examples include imatinib (Gleevec), which incapacitates a mutated enzyme that triggers uncontrolled division of cells in two rare blood and digestive system cancers, and trastuzumab (Herceptin), used to treat breast cancer patients. These drugs have been strikingly successful in providing a few extra weeks of life, before their protective effects wear off and the disease progresses again.
Delivering drugs more precisely to the cancer while sparing normal tissue. One approach is to inject the patient with tiny drug-coated metal beads, which are guided to the tumor by a powerful magnet positioned over the body site. Or, a patient might take light-sensitive drugs that are drawn naturally into rapidly dividing cancer cells. Exposure to certain frequencies of laser light sets off a series of reactions that kill the malignant cells.
Starving cancer cells by cutting off their blood supply. For instance, researchers are testing a drug, called the “icon molecule,” that attacks endothelial cells lining the blood vessels in tumors. However, several clinical studies have found that hypoxic cancer cells sometimes go into a protective mode that produces angiogenic proteins to attract new blood vessels and prompts the cancer cells to become more aggressive.
Other experimental treatments seek to fix defective tumor-suppressor genes and oncogenes, destroy cancer cells with viruses, or signal cancer cells to commit suicide by apoptosis. One promising technique extracts and then infuses hand-picked immune cells (T cells) that have shown an enhanced ability to attack the cancer cells. Additionally, a cancer vaccine (TRICOM) still in clinical studies, contains genetically engineered viruses carrying genes for a cancer protein called carcinoembryonic antigen (CEA). When these proteins are delivered into the patient’s body they stimulate an immune response which then orchestrates an attack on all CEA-bearing cancer cells.
At present, about half of all cancer cases are cured. Although average survival rates have not increased, the quality of life of cancer patients has improved in the last decade. We can offer better treatments for cancer-associated pain, and antinausea drugs and other helpful medicines can soothe the side effects of chemotherapy.
Although once perceived as disorganized cell growth, this disease is now known to be a logical, coordinated process in which a precise sequence of tiny alterations changes a normal cell into a killer. Let’s take a closer look at what cancer really is.
When cells fail to honor normal controls of cell division and multiply excessively, an abnormal mass of proliferating cells called a neoplasm (ne′o-plazm, “new growth”) results. Neoplasms are classified as benign (“kindly”) or malignant (“bad”). A benign neoplasm is strictly a local affair. Its cells remain compacted, are often encapsulated, tend to grow slowly, and seldom kill their hosts if they are removed before they compress vital organs. In contrast, cancers are malignant neoplasms, nonencapsulated masses that grow relentlessly and may become killers. Their cells resemble immature cells, and they invade their surroundings rather than pushing them aside, as reflected in the name cancer, from the Latin word for “crab.” Whereas normal cells become fatally “homesick” and die when they lose contact with the surrounding matrix, malignant cells tend to break away from the parent mass, the primary tumor, and travel via blood or lymph to other body organs, where they survive and form secondary cancer masses. This capability for traveling to other parts of the body, called metastasis (mĕ-tas′tah-sis), probably has a lot to do with cell surface glycoproteins the cancer cells bear. For example, a carbohydrate called sialyl Lewis X binds to adhesion molecules on epithelial cells and platelets. Metastasis and invasiveness distinguish cancer cells from the cells of benign neoplasms. Cancer cells consume an exceptional amount of the body’s nutrients, leading to weight loss and tissue wasting that contribute to death.
Mechanisms of Carcinogenesis
Autopsies on individuals aged 50–70 who died of another cause have revealed that most of them (us) have microscopic (but dormant) in situ neoplasms. So what causes a normal cell to transform or change into a cancerous one? Some physical factors (radiation, mechanical trauma), certain viral infections, chronic inflammations, and many chemicals (tobacco tars, saccharine, some natural food chemicals) can act as carcinogens (cancer-causers). What these factors have in common: They all cause mutations—changes in DNA that alter the expression of certain genes. However, not all carcinogens do damage because most are eliminated by peroxisomal or lysosomal enzymes or by the immune system. Furthermore, one mutation usually isn’t enough; it takes several genetic changes to transform a normal cell into a cancerous cell.
A clue to the role of genes in cancer was provided by the discovery of oncogenes (Greek onco = tumor), or cancer-causing genes, in rapidly spreading cancers. Proto-oncogenes, benign forms of oncogenes in normal cells, were discovered later. Proto-oncogenes code for proteins that are essential for cell division, growth, and cellular adhesion, among other things. Many have fragile sites that break when exposed to carcinogens, converting them to oncogenes. Failure to code for certain proteins may lead to loss of an enzyme that controls an important metabolic process. Oncogenes, now known to number over 100, may also “switch on” dormant genes that allow cells to become invasive and metastasize.
Oncogenes have been detected in only 15–20% of human cancers, so investigators were not too surprised by the discovery of tumor suppressor genes, or antioncogenes, which suppress cancer by inactivating carcinogens, aiding DNA repair, or enhancing the immune system’s counterattack. In fact, over half of all cancers involve malfunction or loss of just two of the 15 identified tumor suppressor genes—p53 and p16. This is not surprising when you learn that p53 prompts most cells to make proteins that put the brakes on cell division in stressed cells by promoting apoptosis or cell cycle arrest. Hence, its impairment invites uncontrolled division and cancer. Furthermore, although each type of cancer is genetically distinct, human cancers appear to share a common master set of genes—an activated group of 67 genes—and almost all cancer cells have gained or lost entire chromosomes. Whatever genetic factors are at work, the “seeds” of cancer do appear to be in our own genes. Thus, cancer is an intimate enemy indeed.
The illustration depicts some of the mutations involved in colorectal cancer, one of the best-understood human cancers. As with most cancers, a metastasis develops gradually. One of the first signs is a polyp, a small benign growth consisting of apparently normal mucosa cells. As cell division continues, the growth enlarges, becoming an adenoma. As various tumor-suppressor genes are inactivated and the K-ras oncogene is mobilized, the mutations pile up and the adenoma becomes increasingly abnormal. The final consequence is colon carcinoma, a form of cancer that metastasizes quickly.
Cancer Prevalence
Almost half of all Americans develop cancer in their lifetime and a fifth of us will die of it. Cancer can arise from almost any cell type, but the most common cancers originate in the skin, lung, colon, breast, and prostate gland. Although stomach and colon cancer incidence is down, skin and lymphoid cancer rates are up.
Many cancers are preceded by observable lumps or other structural changes in tissue—for instance, leukoplakia, white patches in the mouth caused by the chronic irritation of ill-fitting dentures or heavy smoking. Although these lesions sometimes progress to cancer, in many cases they remain stable or even revert to normal if the environmental stimulus is removed.
Diagnosis and Staging
Screening procedures are vital for early detection. Examples include mammography, examining breasts or testicles for lumps, and checking fecal samples for blood. Unfortunately, most cancers are diagnosed only after symptoms have already appeared. In this case the diagnostic method is usually a biopsy: removing a tissue sample surgically and examining it microscopically for malignant cells. Increasingly, diagnosis is made by chemical or genetic analysis of the sample. Typing cancer cells by what genes are switched on or off tells clinicians which drugs to use. For example, taxol, quite successful with breast and ovarian cancer, works only against tumors with a specific genetic makeup. Medical imaging techniques (MRI, CT) can detect large tumors.
Several techniques (physical and histological examinations, lab tests, and imaging techniques) are used to determine the extent of the disease (size of the neoplasm, degree of metastasis, etc.). Then, the cancer is assigned a stage from 1 to 4 according to the probability of cure (stage 1 has the best probability, stage 4 the worst).
Cancer Treatments
Most cancers are removed surgically if possible. To destroy metastasized cells, surgery is commonly followed by radiation therapy (X irradiation and/or treatment with radioisotopes) and chemotherapy (treatment with cytotoxic drugs). Chemotherapy is beset with the problem of resistance. Some cancer cells can eject the drugs in tiny bubbles or flattened vesicles dubbed exosomes, and these cells proliferate, forming new tumors that are invulnerable to chemotherapy. Furthermore, anticancer drugs have unpleasant side effects—nausea, vomiting, hair loss—because they kill all rapidly dividing cells, including normal tissues and cells. X rays also have side effects because, in passing through the body, they destroy healthy tissue in their path as well as cancer cells.
Promising New Therapies
Traditional cancer treatments—”cut, burn, and poison”—are widely recognized as crude and painful. Promising new therapies focus on
Targeted drugs that interrupt the signaling pathways which fuel the cancer’s growth. Examples include imatinib (Gleevec), which incapacitates a mutated enzyme that triggers uncontrolled division of cells in two rare blood and digestive system cancers, and trastuzumab (Herceptin), used to treat breast cancer patients. These drugs have been strikingly successful in providing a few extra weeks of life, before their protective effects wear off and the disease progresses again.
Delivering drugs more precisely to the cancer while sparing normal tissue. One approach is to inject the patient with tiny drug-coated metal beads, which are guided to the tumor by a powerful magnet positioned over the body site. Or, a patient might take light-sensitive drugs that are drawn naturally into rapidly dividing cancer cells. Exposure to certain frequencies of laser light sets off a series of reactions that kill the malignant cells.
Starving cancer cells by cutting off their blood supply. For instance, researchers are testing a drug, called the “icon molecule,” that attacks endothelial cells lining the blood vessels in tumors. However, several clinical studies have found that hypoxic cancer cells sometimes go into a protective mode that produces angiogenic proteins to attract new blood vessels and prompts the cancer cells to become more aggressive.
Other experimental treatments seek to fix defective tumor-suppressor genes and oncogenes, destroy cancer cells with viruses, or signal cancer cells to commit suicide by apoptosis. One promising technique extracts and then infuses hand-picked immune cells (T cells) that have shown an enhanced ability to attack the cancer cells. Additionally, a cancer vaccine (TRICOM) still in clinical studies, contains genetically engineered viruses carrying genes for a cancer protein called carcinoembryonic antigen (CEA). When these proteins are delivered into the patient’s body they stimulate an immune response which then orchestrates an attack on all CEA-bearing cancer cells.
At present, about half of all cancer cases are cured. Although average survival rates have not increased, the quality of life of cancer patients has improved in the last decade. We can offer better treatments for cancer-associated pain, and antinausea drugs and other helpful medicines can soothe the side effects of chemotherapy.
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