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Cancer | Article View | |
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| I. | |
Introduction |
Cancer, new growth of tissue resulting from a continuous proliferation of abnormal cells that have the ability to invade and destroy other tissues.
Cancer, which may arise from any type of cell and in any body tissue, is not a single disease but a large number of diseases classified according to the tissue and type of cell of origin. Several hundred such classes exist, constituting three major subtypes: The first, sarcomas, arise from connective and supportive tissue, such as bone, cartilage, nerve, blood vessels, muscle, and fat. The second, carcinomas, which include the most frequently occurring forms of human cancer, arise from epithelial tissue, such as the skin and the lining of the body cavities and organs, and glandular tissue, such as that of the breast and prostate. Carcinomas with a flaky structure resembling skin are termed squamous-cell carcinomas. Those that resemble glandular tissue are called adenocarcinomas. The third subtype, leukaemias and lymphomas, include the cancers that involve blood-forming tissue and are typified by the enlargement of the lymph nodes, the invasion of the spleen and bone marrow, and the overproduction of immature white blood cells.
| II. | |
Prognosis and the Long-Term Picture |
Many people are now successfully treated for cancer. For example, it is estimated that, out of more than 5 million Americans who have had cancer, 3 million have survived more than five years, and nearly all the survivors can be regarded as cured. The modern approach to cancer treatment also includes an emphasis on the patient’s quality of life—both physical and mental.
There are many forms of cancer where the chances of survival are many times better than they were just a few years ago. Developments in the field of children’s cancers are perhaps the most encouraging. For instance, 90 per cent of children recover from Hodgkin’s disease, whereas 30 years ago only about half survived. Other forms of cancer, such as non-Hodgkin’s disease, some leukaemias, and testicular cancer, can be successfully treated, as can certain forms of non-invasive bladder cancer, which, if detected early, can be contained over a period of several years.
The death rate from cancer has fallen progressively in people under 50, probably because healthier habits and environment have reduced prolonged exposure to carcinogens. Earlier diagnosis, which is absolutely vital in all cases, and improved treatments are also involved. This drop is expected to extend to older age groups as these younger people age.
Decreases in the number of smokers in some countries are starting to have an impact on the cancer figures. For instance, in the United Kingdom the number of deaths from lung cancer in men has finally started to decline. Unfortunately, the number of women dying from it is still going up; Scottish women have the highest rate of death from lung cancer in the world.
The overall risk of death from cancer has increased over the past 30 years. This is because cancer is mainly a disease of older age and, as greater success is achieved at preventing early deaths from other illnesses such as heart disease, more people are living long enough to reach an age where their cancer risk increases.
| III. | |
Occurrence |
Cancer is the leading cause of death in adults in the United Kingdom and the second leading cause of death in adults in the rest of the Western world. In the United Kingdom in 2002 it was responsible for 155,180 deaths; it is also one of the leading causes of death from disease in children between the ages of 1 and 14. However, despite this, it is still rare in young people. In the United Kingdom cancer affects about 1 in 650 children.
The age-adjusted death rate per 100,000 population from all cancers in males is 246.5 in Hungary (one of the highest), as compared to 83.5 in Mexico (one of the lowest). For women, it is 139.8 in Denmark and 62.3 in Mauritius. The rates for England and Wales are 179.2 for males and 125.7 for females; in the United States, the rate is 164.4 for men and 110.6 for women. For particular cancers, the difference between countries may be as high as 40-fold. Evidence from studies of populations that have migrated from one geographical area to another suggests that these variations are due to differences in lifestyle rather than ethnic origin. This is consistent with other evidence that most cancers are predominately related to environmental causes rather than heredity, although the two may interact.
The cancers that cause the most deaths in Europe and the United States are those of the lung, bowel (colorectal), breast, prostate, and stomach. Together they account for about half of cancer deaths. These are also the most common types of cancer along with skin cancer. Skin cancer is the first or second most common cancer in many Western countries such as the United States, Australia, and the United Kingdom. Fortunately, with the exception of malignant melanoma (the rarest and most serious form), skin cancers are rarely fatal.
| IV. | |
How Cancer Occurs |
Cancer is a multi-stage process where a series of irreversible genetic errors occur in a cell in the body during a patient’s lifetime. The early stages (initiation) are critical for setting the process off. Later changes lead to spread and increased growth rate, and are triggered by a range of external factors, known as promoters. These errors may happen because the person has been exposed to cancer-causing agents (carcinogens). For instance, cigarette smoke contains many chemical initiators and promoters.
| A. | |
Gene Defects |
In some people, however, there are also inherited gene defects that can give a potential cancerous cell a head start. Genes are made of deoxyribonulceic acid (DNA—the cell’s chemical “instruction manual”—see Nucleic Acids) and are found in the centre of the cell in structures known as chromosomes. Humans have 23 pairs of chromosomes and over 50,000 genes. If a chromosome is likened to a book, each gene is a paragraph; a fault in a gene may be likened to a misprint.
Every time a cell divides a copy is made of the DNA. Sometimes an error occurs and a new cell ends up with an altered gene—a mutation. If the mutation occurs in a gene that normally controls cell growth, that cell may acquire the potential to become a cancer cell.
A cancerous growth, or neoplasm, is therefore clonal—that is, all its cells are descendants of a single cell. These cells have escaped the control of the normal forces regulating cellular growth. Resembling embryonic cells, they are unable to differentiate or mature into an adult, functioning state. As these cells multiply, they may form a mass known as a tumour, which enlarges and continues to grow without regard to the function of the tissue of origin.
The body has ways of fighting back against mutations and a number of faults has to accumulate before a tumour develops. This can take a long time, which is why cancer is mainly a disease of older people; for instance, 95 per cent of bowel cancers occur in those over 50.
| B. | |
Tumours |
Almost all cancers form tumours, but not all tumours are cancerous, or malignant; the greatest number are benign (not threatening to health). Benign tumours are characterized by entirely localized growth and are usually separated from neighbouring tissue by a surrounding capsule. Benign tumours generally grow slowly, and in structure closely resemble the tissue of origin. In some instances they may endanger the patient by obstructing, compressing, or displacing neighbouring structures, as in the brain. A few benign tumours, such as polyps of the colon, may be precancerous.
| C. | |
Invasion and Spreading |
The most significant attribute of malignant tumours is their ability to spread beyond the site of origin. Cancer may invade neighbouring tissues by direct extension or infiltration, or it may disseminate to distant sites, forming secondary growths known as metastases. The routes and sites of metastases vary with different primary cancers:
(1) When a cancer extends through the surface of the organ of origin into a cavity, cells may break away from the surface and become implanted on the surface of adjacent organs.
(2) Tumour cells may migrate into the lymphatic channels and be carried to the draining lymph nodes, or they may penetrate the blood vessels. Once in the bloodstream, the tumour cells are carried to the point at which the vessels become too small for the large tumour cells to pass. Cells from tumours of the gastrointestinal tract will be stopped in the liver. Later they may go on to the lungs. Cells from all other tumours will go to the lungs before being carried to other organs. The lungs and liver are therefore common sites of metastases.
(3) Many cancers tend to shed cells into the bloodstream early in their course. Most of these cells die in the bloodstream, but some lodge against the surface and penetrate the wall into the tissue. A few may find themselves in a favourable tissue in which they are able to survive and grow into a tumour. Others may divide only a few times, forming a small nest of cells that then remain dormant (a micrometastasis). They may remain dormant for many years, only to begin to grow again as recurrent cancer, for reasons unknown.
Cancer cells, even when widely disseminated, may retain the physical and biological characteristics of their tissue of origin. Thus, a pathologist can often determine the site of origin of metastatic tumours by microscopic examination of the cancerous tissue. Identification of tumours of the endocrine glands, for example, is simplified because they may produce excessive amounts of the hormone that is produced by the parent tissue. Such tumours may also respond to administration of the hormones that normally control that tissue.
In general, the less closely a cancer resembles its tissue of origin, the more malignant and rapidly invasive it tends to be; however, the rate of growth of a cancer depends not only on cellular type and the degree of differentiation from the tissue of origin, but also on various host factors. A characteristic of malignancy is tumour-cell heterogeneity. Because of the abnormalities of proliferation in tumour cells, they are more susceptible to mutation. With time, a tumour tends to become less differentiated and to grow more rapidly. It may also develop increased resistance to chemotherapy or radiotherapy.
| V. | |
Causes, Prevention, and Early Detection |
About 80 per cent of cancers are potentially preventable. The biggest known cause is smoking, which accounts for 30 per cent of deaths from the disease. Although all the causes of cancer are yet to be ascertained, accumulating evidence about the effects of smoking, diet, radiation, hereditary factors, hormones, chemicals, and certain types of infection shows that these factors may be involved.
It is already known that there are several things people can do to cut the risk of cancer. Everyone should:
| A. | |
Smoking |
Smoking is one of the biggest causes of premature death in the Western world. Not only does it cause over one third of cancers, but it also causes heart disease and major forms of lung disease, such as chronic bronchitis and emphysema. Smoking has already killed 60 million people worldwide since 1950 and is likely to kill half a billion of those alive today unless current habits are changed.
In the United Kingdom over 102,000 people die every year from smoking. Fifty thousand of these deaths are from cancer, mostly of the lung: 33,600 people died of lung cancer in the United Kingdom in 2002. Out of 1,000 young adults (if they all smoke), on average 1 will be murdered; 6 will be killed on the roads; and 250 will be killed by smoking in middle age alone.
Smoking causes 90 per cent of lung cancers. It can also cause cancer in a number of other parts of the body, including the mouth, pharynx, larynx, oesophagus, pancreas, renal pelvis, bladder, and cervix.
There can be no doubt that giving up smoking brings down the risk. If a person manages to give up smoking before developing cancer or some other serious disease, most of the risk of dying from smoking-related diseases may be avoided. After ten years the risk will be more than halfway towards that of someone who has never smoked.
| B. | |
Diet |
Diet is probably linked to about 30 to 35 per cent of cancers. Many researchers believe that it plays a part in many of the most common cancers, such as those of the breast and bowel. However, as yet, there is no concrete proof of which elements can cause cancer and which help to protect against it.
At the moment, evidence suggests a protective role for fruit, vegetables, dietary fibre, and certain vitamins. Other factors, such as a high-fat or excessive meat diet, are thought to increase risk. For instance, many researchers think that an increased intake of fresh fruit and vegetables decreases the risk of stomach cancer. People who eat moderate amounts of fruit, such as one piece of fruit per day, have a substantially lower risk of developing this cancer.
Reducing calories from fat to 20 per cent of the diet, cutting down on red meat, increasing dietary fibre (such as wholemeal bread, fruits, and vegetables), and eating protective foods (foods that contain vitamins C and A, as well as vegetables such as cabbage, cauliflower, broccoli, and Brussels sprouts) all provide benefits. Foods (mainly vegetables) containing beta-carotene, an antioxidant that is converted to vitamin A in the body, are thought to provide some protection against the cell changes that may lead to cancer. Moderation in eating salt-cured, smoked, and nitrite-cured foods and in the consumption of alcohol is also advised.
Apart from eating a healthy diet, keeping weight down is also an important measure in cutting cancer risk. Obesity increases the risk of cancers of the breast, bowel, uterus, and prostate. Some recent studies have shown that moderate exercise may also play a part in preventing cancer as well as maintaining general good health.
Over-consumption of alcohol is responsible for 3 per cent of cancer deaths. Cancers of the mouth, throat, and oesophagus are linked to this, with those most at risk being people who drink excessively and smoke cigarettes.
| C. | |
Infections |
There is growing evidence that some infections are linked to certain cancers. In particular, infections have been found to be involved in cancers of the stomach (which killed 6,360 in the United Kingdom in 2002), liver (about 2,510 in 2002), and cervix (about 1,120 in 2002), and in Kaposi’s sarcoma—a rare cancer which occurs in AIDS patients.
The bacterium Helicobacter pylori may help to cause many cases of stomach cancer. Studies have shown that people infected with the bacterium are four times more likely to develop this cancer. In the United Kingdom it has been estimated to help cause as many as half of the approximately 10,000 stomach cancers that occur each year.
Cervical cancer is linked to two sexually transmitted types of human papilloma virus—HPV-16 and HPV-18. HPV infection is quite common and most women who are infected do not develop cervical cancer. However, it does seem that HPV infection is an extremely important step in the development of the disease—often occurring several years before the appearance of cancer. In 2002 it was announced in the US that a vaccine had been developed that was 100 per cent effective against the types of HPV that can lead to cervical cancer. In 2006 it was finally licensed for use in the US, although it can only be given to girls and women between the ages of 9 and 26.
People who are carriers of some types of viruses are at greatly increased risk of cancer. Childhood infection may be particularly important. When viruses like hepatitis B (which contributes to liver cancer) are contracted at birth or during early childhood, the patient becomes a carrier. In countries like China, where childhood infection with hepatitis B is endemic, rates of liver cancer in adults are high—40 to 50 per cent of liver cancer in the world occurs in China. Research is under way to see if vaccinating Chinese children against hepatitis B will prevent them from developing liver cancer in later life.
| D. | |
Hormones |
Certain cancers, particularly of the breast and prostate, have a hormonal link, and some medical researchers think that hormones such as oestrogen may act as tumour promoters in these cancers. Research is continuing into how the growth of cancer cells may be accelerated by hormones and slowed down by hormone-blocking drugs. In June 1999 an 11-year study in the United States concluded that there was no link between hormone replacement therapy (HRT) and non-invasive (earlier stage) breast cancers, or between HRT and the most common forms of invasive (later stage) breast cancers. However, a study of more than 1 million women in the UK between 1996 and 2001 concluded in 2003 that taking the combined oestrogen and progesterone HRT could double the risk of developing breast cancer.
| E. | |
Radiation and Radon |
As well as being a successful treatment for cancer, radiation can cause cancer. The risk from radiation is related directly to the dose received, and therefore for most people the amount received in a lifetime is relatively small. People who live in areas with high levels of radon, a radioactive gas, are more at risk of developing lung cancer. In the United Kingdom radon is thought to be responsible for 6 per cent of lung cancer deaths—making it the second most important cause of lung cancer after smoking.
| F. | |
Sunlight |
Ultraviolet radiation (UV) types A and B from sunlight are responsible for most skin cancers. UVB is at its strongest during the summer months and people need to protect themselves by not exposing the skin for long periods and by wearing a hat with a wide brim that shades the face; by avoiding exposure to the midday sun; and by applying a high-factor sunscreen of at least SPF15 on exposed skin at regular intervals, especially before and after swimming. These precautions apply equally to summer in northern European climates as to summer in hotter ones. Particular attention to this problem in Australia has resulted in health campaigns encouraging people to take precautions against sun exposure.
Skin cancer rates in Australia are higher than anywhere else in the world. It is the most common form of cancer in Australia, affecting all age groups. Most common is basal cell carcinoma (rodent ulcer), which accounts for about 75 per cent of all skin cancers. Squamous-cell carcinomas account for 20 per cent and melanoma, less than 5 per cent. Skin cancers are not common in the young. Melanomas can occur in adolescents but it is very rare for non-melanomas to do so. Melanoma is the most dangerous type of skin cancer. The non-melanomas are rarely fatal, but can be disfiguring.
Two out of three Australians will develop skin cancer—usually a basal cell carcinoma—and about 1 in 60 people will develop a melanoma in his or her lifetime. A major prevention campaign has raised public awareness about skin cancer.
| G. | |
Chemicals |
Certain occupations carry an increased risk of cancer because workers are exposed to hazardous substances such as chemicals, asbestos, or radiation. It is therefore very important for work safety procedures to be put in place, to provide as much protection for workers as possible, and for workers to follow the guidelines.
| H. | |
Hereditary Factors |
It is estimated that 5 to 10 per cent of cancers are inherited, and extensive research is being done to find the faulty genes responsible. Some of these genes have already been found; for instance, the genes BRCA1 and BRCA2 are linked to some hereditary breast cancers. Mutations in BRCA1 are also responsible for about 80 per cent of inherited ovarian cancers. The androgen receptor gene, hAR, and the glutathione s-transferase gene (GST) have both been linked to prostate cancer.
| VI. | |
Detection and Diagnosis |
| A. | |
Symptoms |
The earlier a cancer is diagnosed and treated, the greater the chance that it can be cured. Screening is useful for detecting some cancers, but people still need to be aware of symptoms as cancers may occur between screenings. Everyone should also take notice of the early warning signs of cancers for which there is no screening available. The following list of symptoms warrants attention:
Any of these symptoms, indeed any unexplained lump, pain, weight loss, or lethargy, should be referred to a doctor. Although one or more symptoms may be indicative of something other than cancer, a check-up to confirm their cause is the best course of action.
A physical examination for cancer includes inspection and palpation of all accessible sites, especially the skin, neck, breasts, abdomen, testicles, and lymph-node areas. It may include examination of bodily orifices, particularly rectal examination for cancers of the rectum or prostate, and pelvic examination for cancers of the cervix or uterus.
| B. | |
Screening and Self-Examination |
The earlier a cancer is diagnosed the greater the chance of cure. A monthly check for changes in the way your body looks and feels can help early detection of breast, skin, and testicular cancer. Some cancers can be detected at an early or pre-cancerous stage through screening.
| B.1. | |
Cervical Smear |
Cervical screening can detect cervical cancer. More importantly, it can prevent this cancer because it detects pre-cancerous cells. The United Kingdom has a national screening programme that invites all women between 25 and 64 to have a cervical smear test every three to five years. Over 80 per cent of eligible women have been screened since the scheme started in 1988. Previously, about 1,900 women died of this cancer annually in the United Kingdom, but there was a dramatic 30 per cent decrease in deaths in the 1990s. Doctors are now considering ways of improving the screening programme—including the possibility of adding a test for HPV-16 to the smear test. It is hoped that the vaccine licensed for use in the United States in 2006 could, in the long term, greatly reduce or remove entirely the need for smear tests.
| B.2. | |
Bowel Cancer Screening |
Bowel cancer also has a pre-cancerous stage that can be detected by screening. One method under consideration uses a thin flexible tube (a sigmoidoscope) to detect polyps in the bowel that, if left, may turn cancerous. Studies suggest that removing these benign growths will nearly halve a person’s risk of cancer for about ten years. In 2002 about 16,220 died of cancer of the bowel in the United Kingdom.
A trial is now in progress in the United Kingdom to evaluate this approach. If successful, it could form the basis of a national screening programme. The researchers involved in the study believe that a single screening of people between 50 and 65 may prevent 5,500 of the more than 33,000 cases of bowel cancer that occur every year. Regular screening for this type of cancer is available in other countries, such as Sweden.
| B.3. | |
Breast Cancer Screening |
The United Kingdom has one of the highest death rates from breast cancer in the world. The number of deaths has recently started to decline, but in 2002 some 12,840 women still died of it in the UK and 1 in 12 will continue to develop it at some time.
In 1990 a national screening programme was set up that invites all women between 50 and 65 to have a mammogram (breast X-ray) every three years. Older women can be screened on request. In the United States some doctors recommend that screening should begin at a younger age, but recent studies indicate that mammography may not benefit women prior to the menopause because their breast tissue is more dense, making mammograms consequently much harder to read. In the US, a gene test for early breast cancer detection is under development.
| B.4. | |
Other Cancers |
Ovarian cancer is the fifth most common cancer in women in the United Kingdom; in 2002 it killed about 4,690 women in the UK. It is usually curable when detected at an early stage, with a survival rate of 90 per cent. Unfortunately, many patients do not show symptoms until the cancer has spread. Studies are underway to find the genes involved in this cancer, as it is sometimes familial, and to develop screening methods using ultrasound and blood tests.
Prostate cancer is relatively rare in men under 50, but after this age the incidence rises steeply—faster than any other cancer. Until the late 1990s it was the fourth most common cancer in men, with about 15,000 new cases and 9,500 deaths in the UK in 1998. At that time there was no national screening programme for prostate cancer in the UK. However, the mass introduction of the prostate-specific antigen (PSA) test has allowed the detection and treatment of the cancer at an early stage, leading to fewer deaths. In the United States researchers had found that measuring plasma concentrations of the insulin-like growth factor-1 hormone (IGF-1) could help to identify men who are at high risk of developing prostate cancer, as those with high circulating concentrations of IGF-1 appear to be at higher risk. Asymptomatic screening for prostate cancer uses concentrations of PSA as a screening tool. This earlier detection confirmed the fact that prostate cancer was becoming the most common form of male cancer at the beginning of the 21st century, with 27,000 new cases each year in the UK.
Testicular cancer is the most common form of cancer in young men, occurring mostly in those aged between 15 and 49. It is still relatively rare with just over 1,700 new cases and 106 deaths in the United Kingdom in 2000. It is also one of the most curable cancers; more than 90 per cent of patients make a complete recovery, and when the disease is caught at an early stage survival is almost 100 per cent. There is no screening programme; early detection following self-examination can improve the results of treatment. As there is a wide variation in normal testicular size and shape, it is important for all men from the onset of puberty to be aware of what is normal for them.
| C. | |
Biopsy |
The biopsy remains the only definitive method for the diagnosis of a cancer. In a biopsy, a section of tissue is removed from the tumour itself or from a metastasis. Modern technology has greatly reduced the need for open surgical biopsy. Guided by palpation or a computerized axial tomography (CAT or CT) scan, a tumour in almost any part of the body can be biopsied through a thin, flexible needle. This permits diagnosis before surgery so that the doctor and patient can plan for treatment and surgery, if it is necessary.
| D. | |
Staging |
Once a tissue diagnosis of cancer has been made, the extent, or stage, of the disease must be evaluated because prognosis and appropriate treatment vary with the stage of the disease. For each type of tumour, the stage (I, II, III, or IV) is defined in terms of findings with progressively more severe prognostic implications: small local tumour, more extensive local tumour, regional lymph node involvement, and distant metastases. The clinical stage, defined by information obtained prior to surgical exploration, is used to decide appropriate initial treatment. The surgical stage, which may be different from the clinical, incorporates the findings of the surgical exploration, and is used as a basis for later treatment and for prognosis. It is also used to analyse the effects of different treatments.
| VII. | |
Treatment |
The traditional means of treating cancer have been surgery, radiation, and chemotherapy. However, revolutionary treatments are now under development and researchers are using laboratory discoveries to design drugs that will exploit specific biological processes in cancer.
| A. | |
Surgery |
The principal approach to curing cancer is to remove all the malignant cells by a surgical operation. In the past this meant the removal of all of the involved tissue and as much potentially involved tissue as possible, including adjacent tissues and lymph nodes. For some tumours, notably cancer of the breast, this radical degree of surgery (see mastectomy) is not always necessary.
Refinements in surgical techniques, improved knowledge of physiology, advances in anaesthesia, ready availability of blood products, and potent antibiotics have permitted less extensive surgery with more rapid recovery and less resulting disability. Many cancers, though, are at too advanced a stage at the time of diagnosis to be eradicated by surgery. If local extension involves neighbouring tissues that cannot be sacrificed, or if distant metastases are already present, surgery will not cure the cancer. Even when it is clear that surgical cure is not possible, however, surgery may help to relieve symptoms, such as obstruction, or to reduce the size of the tumour in an effort to improve the patient’s response to subsequent radiotherapy or chemotherapy.
| B. | |
Radiation Therapy |
Ionizing radiation, which may be either electromagnetic or particulate, is destructive to tissue. Electromagnetic radiation includes gamma rays, which are emitted by radioactive decay, and X-rays, which are produced when a beam of electrons strikes a heavy-metal target. Particulate radiation includes beams of electrons, protons, neutrons, alpha particles (helium nuclei), and negative pi mesons (pions).
Tumours vary greatly in their sensitivity to radiation. A “sensitive” tumour is one that is more sensitive than surrounding normal tissues. When such a tumour is readily accessible—a superficial tumour, for example, or one in an organ like the uterus, into which a radiation source can be introduced—it may be curable by radiation therapy. Because of its relatively sparing effect on normal tissues, radiation is useful when a tumour cannot be removed because surgery would damage vital adjacent tissue, or because it has begun to infiltrate adjacent structures that cannot be sacrificed. Radiation therapy is also extremely useful for palliation (temporary relief), especially of metastatic tumours.
Radiation can also be a valuable adjunct to surgery. Pre-operative radiation may rapidly sterilize the tumour cells and prevent them from seeding at surgery. It may also shrink the tumour and make surgery easier, or shrink an inoperable tumour so that it becomes operable. In other tumours, post-operative radiation is used.
A major risk of radiation therapy, however, is that the application of high doses to a cancerous organ can damage adjacent organs where there are no tumour cells. In 2001 doctors in Italy treated a cancer by removing an entire organ (a liver), administering radiotherapy, and then re-implanting the organ back into the body. Although a year later the liver was still functioning normally, the procedure is many years away from becoming a widely available option.
| C. | |
Chemotherapy |
Chemotherapy is the use of drugs in the treatment of cancer. Since a drug is distributed throughout the body by the bloodstream, chemotherapy is prescribed for tumours that have spread beyond the area accessible by surgery or radiotherapy. A number of different types of anti-cancer drugs are used, but nearly all work by interfering with DNA synthesis or function. Rapidly dividing cells are therefore more sensitive to chemotherapy.
| C.1. | |
Cell Sensitivity |
Cancers have a larger proportion of dividing cells than do normal tissues, in which stem, or replenishing, cells are dormant. This means that normal cells are more resistant to drug effect than the cancer cells, which proliferate rapidly. The most rapidly proliferating normal cells are in the bone marrow and the lining of the gastrointestinal tract. These are the most sensitive normal areas likely to be affected by chemotherapy and therefore constitute the sites of toxicity that will limit the tolerable dose of most drugs.
Therefore, to be effectively treated, a tumour must have a sensitivity greater than that of the most sensitive normal tissue. Some tumours may be many times more sensitive, but many are only slightly more sensitive. Fortunately, the normal bone marrow cells can divide faster than malignant cells and thus recover more rapidly. This permits a repeat cycle of the drug before the tumour has regrown to any great extent. Repeated cycles can steadily deplete a tumour before resistance occurs.
Some tumours are so sensitive to chemotherapy that a chemotherapeutic cure is possible in a high percentage: uterine cancer; acute lymphoblastic leukaemia, especially in children; Hodgkin’s disease; testicular carcinoma; and several childhood cancers are examples. These cancers have often already spread at the time of diagnosis and cannot be treated by other means. However, other advanced cancers respond well to chemotherapy and can be controlled for a long time, so chemotherapy is commonly used for palliation.
| C.2. | |
Toxicity and Resistance |
The two major problems limiting the usefulness of chemotherapy are toxicity and resistance. Techniques that avoid or control toxicity and reduce the risk of resistance have steadily improved. It is important to begin treatment as early as possible, to use the optimal dose of the drug, and to repeat cycles as quickly as possible, while giving the patient a chance to recover somewhat from toxicity.
The use of multiple drugs is effective. Combination chemotherapy employs several drugs (often three to six at a time), each of which is effective as a single agent. The drugs used have different mechanisms of action, making cross-resistance less likely, and different types of toxicity, so that each may be given at optimal dose without causing fatal additive toxicity.
| C.3. | |
Chemotherapy with Other Treatments |
High doses of chemotherapy can be given if a bone marrow transplant or bone marrow or stem cell rescue is part of the treatment regime. This is most often used in leukaemia treatment, but there are trials under way in other cancers.
Chemotherapy may also be used with surgery or radiation as combined modality therapy. It is often used as an adjuvant, or helper, when surgery is the primary therapy. As such it is usually given after surgery. This type of therapy has greatly increased the cure rate of breast cancer. The major purpose of chemotherapy as an adjuvant is to kill off micrometastases that may have been established before surgery.
Recently, chemotherapy has been used before surgery as a neo-adjuvant. This therapy has the same effect as adjuvant chemotherapy but may also shrink a tumour, making it more easily operable.
| D. | |
Hormone Therapy |
Many cancers arising from tissues that are hormone-dependent, such as the breast, prostate, endometrium (uterine lining), and thyroid, are responsive to hormone manipulation. This may consist of removing the source of the stimulating hormone or the administration of various hormones, antihormones, and hormone blockers, such as tamoxifen.
| E. | |
Other Approaches |
Several promising new approaches to the treatment of cancer are being taken. In one, biological agents known as biological response modifiers are used to modify the response of the body (particularly the immune system) to cancer. Another approach involves biological agents that stimulate certain cells, which can then attack the malignant cells. The best example is the use of interleukin-2 to stimulate the patient’s lymphokine-activated killer lymphocytes (LAK cells).
Research is also concerned with tumour-specific antigens, against which antibodies could be raised. These anti-tumour antibodies would be used to treat cancer either directly or by coupling to a chemotherapeutic agent. The antibody could identify the malignant cell and stick to it, thus delivering the drug directly to the target.
For example, a new drug under development blocks the enzyme that destroys the connective material between cells, which furthers the spread of the cancer. The drug thereby prevents cancer cells breaking away from the tumour and spreading to other parts of the body.
| F. | |
Other New Approaches |
Another growing area of research is gene therapy. This employs various methods to introduce genetic material into the cancer to make it more recognizable to the immune system. It can also make the cancer cells more sensitive to drug treatments, or it can place new genes into T-cells to make them more active. Specific types of human cells, such as breast and prostate cells, could be genetically modifed to determine which particular genetic changes cause cancer. Such knowledge could then be used to identify people at increased risk for certain cancers. Specialized drugs could be produced that will target specific genetic flaws linked to cancer.
Work is also under way to develop vaccines by removing cells from the patient and modifying them in the laboratory so that they secrete a protein that stimulates the immune system. The cells are irradiated to stop them dividing, and are then injected into the patient.
Even if cured, a cancer patient may be left with serious disabilities. Every effort must be made to achieve the maximum possible quality of life through rehabilitative techniques, including reconstructive surgery. For the patient who is not cured, palliative therapy may achieve comfort and good function for months or years. Pain can be a severe problem, as can depression, but both can be relieved today much more than in the past.
