Cancer

Cancer: Approximately one out of every two American men and one out of every three American women would face the reality of some type of cancer at some point during the course of their life. Cancer usually is a disease of the elderly population and 77 percent of cancers occur in people above age 55 or older. Cancer has two peaks one peak in the early childhood and the other after 55 years. There is no age period during which one is completely free from the risks of cancer, however the incidence of cancer tends to become lower past the teenage. Some cancers occur predominantly in the elderly, other types occur in children, Cancer occurs in all ethnic races, however the cancer rates and rates of specific cancer types may vary from group to group. Late stages of cancer may be incurable in most cases, but with the advancement of medicine, more and more cancers are becoming curable. Cancer may be curable if detected early in the course of the disease. Millions of people are living today with cancer or as cancer survivors. Early detection of cancer is very important because the generally earlier the cancer is detected higher the chance for cure.

All living things are made up of cells. Cells are the basic living units. Some living things like amoeba may have one cell only while a complex animal like a cat may have billions of cells in the body. Many cells divide to produce daughter cells. This is required for the replacement of cells lost during the course of life. The process of cell division is a very tightly controlled process and occurs in the body only to the extent needed in any particular situation. During the process of cell division one cell may acquire some genetic mutation that would alter the cell division control mechanisms of that cell. This altered cell no longer listens to the control signals for cell division and may continue to divide and multiply. This uncontrolled cell division and growth ultimately results in cancer.

Cancer is characterized by uncontrolled cell division and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue (invasion) or by migration of cells to distant sites (metastasis). This unregulated growth is caused by damage to DNA, resulting in mutations to vital genes that control cell division, among other functions. One or more of these mutations, which can be inherited or acquired, can lead to uncontrolled cell division and tumor formation. Tumor ("swelling" in Latin) refers to any abnormal mass of tissue, but may be either cancerous (malignant) or non-malignant (nonmalignant). Only cancerous tumors are capable of invading other tissues or metastasizing.

Cancer can cause a number of different symptoms, depending on the site and character of the malignancy and whether there is metastasis. A definitive diagnosis commonly requires the microscopic examination of tissue obtained by biopsy. Once diagnosed, cancer is commonly treated with surgery, chemotherapy and/or radiation.

If untreated, most cancers eventually cause death; cancer is one of the leading causes of death in developed countries. Most cancers can be treated and a number of cured, particularly if therapy begins early. A number of forms of cancer are associated with environmental factors, which may be avoidable. Smoking tobacco leads to more cancers than any other environmental factor.

Diagnosing cancer

Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which commonly requires a biopsy. Some cancers are discovered accidentally during medical evaluation of an unrelated problem.

Signs and symptoms

Roughly, cancer symptoms can be divided into three groups:

• Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice.
• Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Eventhough advanced cancer may cause pain, it is often not the first symptom.
• Systemic symptoms: weight loss, poor appetite and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every single item in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

Biopsy

A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by microscopic examination of the malignant cells by a pathologist. The procedure of obtaining cells and/or pieces of tissue, and their examination, is referred to as a biopsy. The tissue diagnosis indicates the type of cell that is proliferating, its severity (degree of dysplasia), and its extent and size. Cytogenetics and immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best therapy.

All cancers can be cured if entirely removed, and sometimes this can be accomplished by the biopsy procedure. When the whole mass of abnormal tissue (the "lesion") is removed, the borders of the sample are examined closely to see if all cancerous tissue has truly been excised. If the cancer has spread to other sites in the body (metastasis), complete surgical excision is impossible.

The nature of the biopsy depends on the organ that is sampled. A number of biopsies (such as those of the skin, breast or liver) can happen on an outpatient basis. Biopsies of other organs are performed under anesthesia and require surgery.

Screening

Cancer screening is a test to detect unsuspected cancers in the population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive followup tests are performed to confirm the diagnosis.

Screening for cancer can lead to earlier diagnosis. Early diagnosis may lead to extended life. Many different screening tests have been developed. Breast cancer screening can be done by breast self-examination. Screening by regular mammograms detects tumors even earlier than self-examination, and a number of countries use it to systematically screen all middle-aged women. Colorectal cancer can be detected through fecal occult blood testing and colonoscopy, which reduces both colon cancer incidence and mortality, presumably through the detection and removal of precancerous polyps. Similarly, cervical cytology testing (using the Pap smear) leads to the identification and excision of premalignant lesions. Over time, such testing has been followed by a dramatic reduction of cervical cancer incidence and mortality. Testicular self-examination is recommended for men beginning at the age of 15 years to detect testicular cancer. Prostate cancer can be screened for by a digital rectal exam along with prostate specific antigen (PSA) blood testing.

Screening for cancer is controversial in cases when it is still not known if the test actually saves lives. The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer therapys. For example: when screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to therapy. This situation, called overdiagnosis, puts men at risk for complications from unnecessary therapy such as surgery or radiation. Followup procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer therapy may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). Similarly, for breast cancer, there have recently been criticisms that breast screening programs in some countries cause more problems than they solve. This is because screening of women in the general population will result in a large number of women with false positive results which require extensive follow-up investigations to exclude cancer, leading to having a high number-to-treat (or number-to-screen) to prevent or catch a single case of breast cancer early.

Cervical cancer screening via the Pap smear has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being a cancer, it has clear risk factors (sexual contact), and the natural progression of cervical cancer is that it normally spreads slowly over many years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.

For these reasons, it is important that the benefits and risks of diagnostic procedures and therapy be taken into account when considering whether to undertake cancer screening.

Use of medical imaging to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an incidentaloma - a non-malignant lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations.

Types of cancer

Cancer cells within a tumor are the descendants of a single cell, even after it has metastasized. Hence, a cancer can be classified by the type of cell in which it originates and by the location of the cell.

Carcinomas originate in epithelial cells (e.g. the digestive tract or glands). Hematological malignancies, such as leukemia and lymphoma, arise from cells of heamatopoeitc origin, such as blood and bone marrow. Sarcoma arises from connective tissue, bone or muscle. Cancerous tumors commonly end in suffix "-carcinoma" for epithelial cancers, and "-sarcomas" for connective tissue tumors. Otherwise, non-malignant tumors of both origins are denoted as "-omas." For instance, non-malignant tumor of fat cells are known as "lipoma," while its cancerous form is known as "liposarcoma."

Adult cancers

In the USA and other developed countries, cancer is presently responsible for about 25% of all deaths

For adult males in the United States, the most common cancers are prostate cancer (33% of all cancer cases), lung cancer (13%), colorectal cancer (10%), bladder cancer (7%) and cutaneous melanoma (5%). As a cause of death lung cancer is the most common (31%) cause, followed by prostate cancer (10%), colorectal cancer (10%), pancreatic cancer (5%) and leukemia (4%)

For adult females in the United States, breast cancer is the most common cancer (32% of all cancer cases) followed by lung cancer (12%), colorectal cancer (11%), endometrial cancer (6%, uterus) and non-Hodgkin's lymphoma (4%). By cause of death, lung cancer is again the most common (27% of all cancer deaths), followed by breast cancer (15%), colorectal cancer (10%), ovarian cancer (6%) and pancreatic cancer (6%)

These statistics vary substantially in other countries.

Other cancers not mentioned:

• Epithelial tumors: skin cancer (this is in fact the most common cancer but often not classified as such in health statistics), cervical cancer, anal carcinoma, esophageal cancer, hepatocellular carcinoma (in the liver), laryngeal cancer, renal cell carcinoma (in the kidneys), stomach cancer, a number of testicular cancers, and thyroid cancer.
• Hematological malignancies (blood and bone marrow): leukemia, lymphoma, multiple myeloma.
• Sarcomas: osteosarcoma (in bone), chondrosarcoma (arising from cartilage), rhabdomyosarcoma (in muscle)
• Miscellaneous origin: brain tumors, gastrointestinal stromal tumors (GIST), mesothelioma (in the pleura or pericardium), thymoma and teratomas, melanoma

Childhood cancers

Cancer can also occur in young children and adolescents. Here, the aberrant genetic processes that fail to safeguard against the clonal proliferation of cells with unregulated growth potential occur early in life and can progress quickly.

The age of peak incidence of cancer in children occurs during the first year of life. Leukemia (commonly ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma

Female infants and male infants have essentially the same overall cancer incidence rates, but white infants have substantially higher cancer rates than black infants for most cancer types. Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.

Causes and pathophysiology

Origins of cancer

Cell division (proliferation) is a physiological process that occurs in almost all tissues and under a number of circumstances. Normally the balance between proliferation and cell death is tightly regulated to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer disrupt these orderly processes.

The uncontrolled and often rapid proliferation of cells can lead to either a non-malignant tumor or a cancerous tumor (cancer). Non-cancerous tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they extrinsically compress vital structures. Cancerous tumors can invade other organs, spread to distant locations (metastasize) and become life-threatening.

Molecular biology

Carcinogenesis (meaning literally, the creation of cancer) is the process of derangement of the rate of cell division due to damage to DNA.

Cancer is, ultimately, a disease of genes. Carcinogenesis commonly requires multiple mutations in a number of genes, thus mutations in single gene is simply not enough. A cell divides without any regulatory manner when is normal program of proliferation is disrupted, and oftentimes these disruptions are about promotion of mitogenic signals and suppression of anti-mitogenic signals. These two processes involve oncogenes, and tumor suppressor genes, respectively.

Proto-oncogenes, broadly defined, are genes whose gene products promote cellular growth. These products can be hormones, mitogens, cell surface receptors, members of intracellular signaling pathways, and transcription factors. Oftentimes mutations in these proto-oncogenes cause them to become overactive, thus signalling the cells to divide and undergo uncontrolled growth.

Tumor suppressor genes typically encode for anti-proliferation signals and proteins that suppresses mitosis. Generally tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Their main function is to arrest the progression of cell cycle before any DNA damage is repared. Otherwise, these genetic lesions, which may contribute to further genomic instability, may be passed on to daughter cells. Canonical tumor suppressors include p53, which is a transcription factor activated by a number of cellular stress including hypoxia and UV damage.

In general, mutations in both types of genes are mandatory for cancer to occur. For example, a mutation limited to one oncogene would be suppressed by normal mitosis control (the Knudson or 1-2-hit hypothesis) and tumor suppressor genes. A mutation to only one tumor suppressor gene would not cause cancer either, due to the presence of a number of "backup" genes that duplicate its functions. It is only when enough proto-oncogenes have mutated into oncogenes, and enough tumor suppressor genes deactivated or damaged, that the signals for cell growth overwhelm the signals to regulate it, that cell growth quickly spirals out of control.

On a genetic side note, mutations in proto-oncogenes are dominant, or gain of function mutations, while mutations in tumor suppressors are recessive, or loss of function mutations. Each cell has two copies of a same gene (one inherited from each parent), and under most cases gain of function mutation in one copy of a particular proto-oncogene is enough to make that gene a true oncogene, while commonly loss of function mutation need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, there are cases in which one loss of function copy of a tumor suppressor gene can render (or poison) the other copy non-functional, and this is called dominant negative effect, and this is observed in a number of p53 mutations.

Tumor suppressors are indicated in a number of families with hereditary cancers. Members within these families have increased incidence and decreased latency of multiple tumors. The mode of inheritance of mutaant tumor suppressors is that affected member inherits a defective copy from one parent, and a wildtype (normal) copy from another. Because mutations in tumor suppressers act in recessive manner (note, however, there are exceptions), the loss of the wildtype copy creates the cancer phenotype. For instance, individuals who are heterozygous for p53 mutations are often victims of Li-Fraumeni Syndrome, and those who are heterozygous for Rb are victims of retinoblastoma. Similarly, APC is linked to adenopolyposis colon cancer (thousands of polyps in colon while young), while BRCA to early onset of breast cancer (often bilateral).

Cancer is ultimately due to accumulation of genetic insults, which are fundamentally mutations in the DNA. Substances that cause these mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. Tobacco smoking is associated with lung cancer. Breathing asbestos fibers is associated with mesothelioma. Prolonged exposure to radiation, especially ultraviolet radiation from the sun, leads to melanoma and other skin malignancies.

Even though most carcinogens are mutagens, some carcinogens are not. For instance estrogen is mandatory for proliferation in a subset of breast tumor (estrogen-dependent BC), even though estrogen does not induce DNA damage. These mitogens promote cancers through their stimulatory effect on the rate of cell mitosis. Faster rates of mitosis increasingly leave less time for DNA repaire, therefore increasingly the likelihood of a genetic mistake being passed onto daughter cells, which in turn accumulates multiple mutations that may lead to carcinogenesis or progression of the disease.

Furthermore, a number of cancers are viral in origin; this is particularly true in animals such as birds, but less so in humans. The mode of virally-induce tumors can be divided into two, acutely or slowly- transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for a overactive oncogene called viral-oncogene (or v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, virus genome is inserted (viral genome insertion is obligatory part of retroviruses) near a proto-oncogene in the host genome and the viral promoter or other transcription regulatory elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-onc is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming virus, which already carries the v-onc.

Most cases the etiology of cancer is unknown. However, with the help of molecular biological and gross karyotyping techniques, it is possible to characterize the mutations and chromosomal aberrations of tumor cells, and rapid progress is being made in prognosis based on the type and spectrum of mutations in some cases. For example, up to half of all tumors have a defective p53 gene, a tumor suppressor gene also known as "the guardian of the genome". This mutation is associated with poor prognosis, since those tumor cells are less likely to go into apoptosis (programmed cell death) when cells are challenged by chemotherapeutics and radiation.

Cancerous tumors cells have distinct properties (examples):

• evading apoptosis (down-regulation of death ligands in tumor cells)
• unlimited growth potential (immortalitization) (loss of regulatory region of receptor)
• self-sufficiency of growth factors (see above)
• insensitivity to anti-growth factors (see above)
• increased cell division rate (loss of Rb, which induces mitosis arrest)
• altered ability to differentiate (expression of embryonic markers)
• no ability for contact inhibition (down-regulation of E-cadherin, a celllular adhesion molecule)
• ability to invade neighbouring tissues (expression of metalloproteinases, which break down extracellular matrix)
• ability to build metastases at distant sites
• ability to promote blood vessel growth (angiogenesis) (expression of VEGF)

Morphology

Cancer tissue has a distinctive appearance under the microscope. Among the distinguishing traits are a large number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, loss of normal tissue organization, and a poorly defined tumor boundary. Immunohistochemistry and other molecular methods may characterise specific markers on tumor cells, which may aid in diagnosis and prognosis.

Biopsy and microscopical examination can also distinguish between malignancy and hyperplasia, which refers to tissue growth based on an excessive rate of cell division, leading to a larger than usual number of cells but with a normal orderly arrangement of cells within the tissue. This process is considered reversible. Hyperplasia can be a normal tissue response to an irritating stimulus, for example callus.

Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure. Often such cells revert back to normal behavior, but occasionally, they gradually become cancerous.

The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and shows no propensity to invade other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is commonly removed surgically, if possible.

Heredity

Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, many recognised syndromes of cancer with a hereditary component. Examples are:

• certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovary cancer
• tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)
• Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft-tissue sarcoma, brain tumors) due to mutations of p53
• Turcot syndrome (brain tumors and colonic polyposis)
• Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
• Retinoblastoma in young children is an inherited cancer

Environment and diet

The most consistent finding, over decades of research, is the strong association between tobacco use and cancers of a number of sites. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men. Up to half of all cancer cases can be attributed to smoking, diet, and environmental pollution.

Treatment of cancer

Cancer can be treated by surgery, chemotherapy, radiation treatment, immunotherapy or other methods. The choice of treatment depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). Many experimental cancer therapys are also under development.

Complete removal of the cancer without damage to the rest of the body is the goal of therapy. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.

Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single therapy for all infectious diseases.

Surgery

If the tumor is localized, surgery is often the preferred therapy. Example procedures include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. Since a single cancer cell can grow into a sizable tumor, removing only the tumor leads to a greater chance of recurrence. A margin of healthy tissue is often resected to make sure all malignant tissue is removed.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether there has been metastasis to regional lymph nodes. Staging determines the prognosis and the need for adjuvant treatment.

Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative therapy.

Chemotherapy

Chemotherapy is the therapy of cancer with drugs ("anticancer drugs") that can destroy cancer cells. It interferes with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells. Hence, chemotherapy has the potential to harm healthy tissue, particularly those tissues that have a high replacement rate (e.g. intestinal lining). These cells commonly repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

A novel technique involves taking samples of the patient's tissue before chemotherapy. These tissues samples are screened to ensure they do not contain malignant cells. The samples are expanded using tissue engineering techniques, and are then re-implanted following high dose chemotherapy in order to recolonise the damaged and somewhat destroyed tissue. A variation upon this method uses allogenic samples (samples donated by a different donor) instead of the patient's own tissue

Immunotherapy

Immunotherapy is the use of immune mechanisms against tumors. These are used in various forms of cancer, such as breast cancer (trastuzumab/Herceptinandreg;) but also in leukemia (gemtuzumab ozogamicin/Mylotargandreg;). The agents are monoclonal antibodies directed against proteins that are characteristic to the cells of the cancer in question, or cytokines that modulate the immune system's response.

Radiation treatment

Radiation treatment (also called radiotherapy, X-ray treatment, or irradiation) is the use of a certain type of energy (called ionizing radiation) to kill cancer cells and shrink tumors. Radiation treatment injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Eventhough radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation treatment is to damage as a number of cancer cells as possible, while limiting harm to nearby healthy tissue.

Radiation treatment may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, spine, stomach, uterus, or soft tissue sarcomas. Radiation can also be used to treat leukemia and lymphoma (cancers of the blood-forming cells and lymphatic system, respectively). Radiation dose to each site depends on many factors, including the type of cancer and whether there are tissues and organs nearby that may be damaged by radiation. recent issue of bla bla bla. This is the recent issue of bla bla bla

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Hormonal suppression

The growth of nearly all tissues, including cancers, can be accelerated or inhibited by providing or blocking certain hormones. This allows an additional method of therapy for a number of cancers. Common examples of hormone-sensitive tumors include certain types of breast, prostate, and thyroid cancers. Removing or blocking estrogen, testosterone, or TSH, respectively, is often an important additional therapy.

Symptom control

Eventhough the control of the symptoms of cancer is not typically thought of as a therapy directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other therapys. Eventhough all practicing doctors have the therapeutic skills to control pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of palliative care has arisen specifically in response to the symptom control needs of this group of patients.

Analgesia (painkillers, frequently opioids such as morphine) and antiemetics (drugs to suppress nausea and vomiting) are very usually used in patients with cancer-related symptoms.

Treatment trials

Clinical trials, also called research studies, test new therapys in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test a number of types of therapy such as new drugs, new approaches to surgery or radiation treatment, new combinations of therapys, or new methods such as gene treatment.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new therapys begins in the laboratory, where researchers first develop and test new ideas. If an approach seems promising, the next step may be testing a therapy in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, therapys that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising therapys are safe and effective.

Patients who take part may be helped personally by the therapy(s) they receive. They get up-to-date care from cancer experts, and they receive either a new therapy being tested or the best available standard therapy for their cancer. Of course, there is no guarantee that a new therapy being tested or a standard therapy will produce good results. New therapys also may have unknown risks, but if a new therapy proves effective or more effective than standard therapy, study patients who receive it may be among the first to benefit.

Complementary and alternative medicine

Complementary and alternative medicine (CAM) therapys are the diverse group of medical and health care systems, practices, and products that are not presently considered to be effective by the standards of conventional medicine. Some non-conventional therapy methods are used to "complement" conventional therapy, to provide comfort or lift the spirits of the patient, while others are offered as alternatives to be used instead of conventional therapys in hope of curing the cancer.

Common complementary measures include prayer or psychological approaches such as "imaging." A number of people feel these approaches benefit them, but most have not been scientifically proven and therefore face skepticism. Other complementary approaches include traditional medicine like Traditional Chinese Medicine.

A wide range of alternative therapys have been offered for cancer over the last century. The appeal of alternative cures arises from the daunting risks, costs, or potential side effects of a number of conventional therapys, or in the limited prospect for cure. Proponents of these therapies are unable or unwilling to demonstrate effectiveness by conventional criteria. Alternative therapys have included special diets or dietary supplements (e.g., the "grape diet" or megavitamin treatment), electrical devices (e.g., "zappers"), specially formulated compounds (e.g., laetrile), unconventional use of conventional drugs (e.g., insulin), purges or enemas, or physical manipulations of the body. Some of these therapys meet all the criteria for fraud. Collectively they are referred to by skeptics as cancer quackery. An extensive, explanatory catalog of these therapys is available at Quackwatch [1]. Almost all physicians recommend against using these modalities as sole therapy for potentially fatal conditions such as cancer.

Epidemiology

In some Western countries, such as the USA and the UK², cancer is overtaking cardiovascular disease as the leading cause of death. In a number of Third World countries cancer incidence (insofar as this can be measured) appears much lower, most likely because of the higher death rates due to infectious disease or injury. With the increased control over malaria and tuberculosis in some Third World countries, incidence of cancer is expected to rise; this is termed the iceberg phenomenon in epidemiological terminology.

Cancer epidemiology closely mirrors risk factor spread in various countries. Hepatocellular carcinoma (liver cancer) is rare in the West but is the main cancer in China and neighboring countries, most likely due to the endemic presence of hepatitis B and aflatoxin in that population. Similarly, with tobacco smoking becoming more common in various Third World countries, lung cancer incidence has increased in a parallel fashion.

Prevention

Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, therapy of precancerous lesions).

Much of the promise for cancer prevention comes from observational epidemiologic studies that show associations between modifiable life style factors or environmental exposures and specific cancers. Evidence is now emerging from randomized controlled trials designed to test whether interventions suggested by the epidemiologic studies, as well as leads based on laboratory research, actually result in reduced cancer incidence and mortality.

Examples of modifiable cancer risk include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption, being physically active, and maintaining recommended body weight may all contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexual and reproductive practices, the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, certain occupational and chemical exposures, and infectious agents.

Diet and cancer

The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States). Studies have shown that immigrants develop the risk of their new country, suggesting a link between diet and cancer rather than a genetic basis.

Despite frequent reports of particular substances (including foods) having a beneficial or detrimental effect on cancer risk, few of these have an established link to cancer. These reports are often based on studies in cultured cell media or animals. Public health recommendations cannot be made on the basis of these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.

The case of beta-carotene provides an example of the necessity of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was especially strong in lung cancer. This hypothesis led to a series of large randomized trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but significantly, increased in smokers, leading to an early termination of the study

Other chemoprevention agents

Daily use of tamoxifen, a selective estrogen receptor modulator, for up to 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. Cis-retinoic acid also has been shown to reduce risk of second primary tumors among patients with primary head and neck cancer. Finasteride, a 5-alpha reductase inhibitor, has been shown to lower the risk of prostate cancer. Other examples of drugs that show promise for chemoprevention include COX-2 inhibitors (which inhibit a cyclooxygenase enzyme involved in the synthesis of proinflammatory prostaglandins).

Cancer vaccines

Considerable research effort is now devoted to the development of vaccines (to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific epitopes) and to potential venues for gene treatment for individuals with genetic mutations or polymorphisms that put them at high risk of cancer. No cancer vaccines are presently in use, and most of the research is still in its initial stages.

As of October 2005, scientists found that an experimental vaccine for HPV types 16 and 18 was 100% successful at preventing infection with these types of HPV and, thus, are able to prevent the majority of cervical cancer cases. [2]

Genetic testing

Genetic testing for high-risk individuals, with enhanced surveillance, chemoprevention, or risk-reducing surgery for those who test positive, is already available for certain cancer-related genetic mutations.

Coping with cancer

A number of local organizations offer a variety of practical and support services to people with cancer. Support can take the form of support groups, counseling, advice, financial assistance, transportation to and from therapy, or information about cancer. Neighborhood organizations, local health care providers, or area hospitals are a good place to start looking.

While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and sexuality.

A number of governmental and charitable organizations have been established to help patients cope with cancer. These organizations often are involved in cancer prevention, cancer therapy, and cancer research. Examples include: American Cancer Society, BC Cancer Agency, Macmillan Cancer Relief , the Terry Fox Foundation, Cancer Research UK, Canadian Cancer Society, International Agency for Research on Cancer and the National Cancer Institute (US).

Social impact

Cancer has a reputation for being a deadly disease. While this certainly applies to certain particular types, this is otherwise a generalization. Some types of cancer have a prognosis that is substantially better than noncancerous diseases such as heart failure and stroke.

Progressive and disseminated cancerous disease has a substantial impact on a cancer patient's quality of life, and a number of cancer therapys (such as chemotherapy) may have severe side-effects. In the advanced stages of cancer, a number of patients need extensive care, affecting family members and friends. Palliative care solutions may include permanent or "respite" hospice nursing.

Cancer research

Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. While understanding of cancer has increased exponentially since the last decades of the 20th century, radically new therapies are only discovered and introduced gradually.

Inhibitors of tyrosine kinases (imatinib and gefitinib) in the late 1990s were considered a major breakthrough; these interfere specifically with tumor-specific proteins. Monoclonal antibodies have proven to be another major step in oncological therapy.

References

• Note 1: Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CACancer J Clin 2005;55:10-30. Fulltext. PMID 15661684.
• Note 2: Cancer: Number one killer (9 November, 2000). BBC News online
• Note 3: Questions and Answers About Beta Carotene Chemoprevention Trials
• Note 4: Bilal A, Treating Cancer with Stem Cells, Medical Engineer, 25 July 2005 Fulltext

External links

• Cancer Blog