More dangerous, or malignant, tumors form when two things occur:
When a tumor successfully spreads to other parts of the body and grows, invading and destroying other healthy tissues, it is said to have metastasized. This process itself is called metastasis, and the result is a serious condition that is very difficult to treat.
According to the American Cancer Society, Cancer is the second most common cause of death in the US and accounts for nearly 1 of every 4 deaths. The World Health Organisation estimates that, worldwide, there were 4 million new cancer cases and 8.2 million cancer-related deaths in 2012 (their most recent data).
There are said to be over 200 different types of cancer. We have the following common cancer types covered in individual Knowledge Center articles:
We are a leading publisher of worldwide cancer news and research. You can find all our latest news in our cancer news section.
The rest of this article will focus on what cancer is, what causes cancer, the symptoms, diagnosis and available treatments.
Fast facts on cancer
Here are some key points about cancer. More detail and supporting information is in the main article.
Scientists reported in Nature Communications (October 2012 issue) that they have discovered an important clue as to why cancer cells spread. It has something to do with their adhesion (stickiness) properties. Certain molecular interactions between cells and the scaffolding that holds them in place (extracellular matrix) cause them to become unstuck at the original tumor site, they become dislodged, move on and then reattach themselves at a new site.
The researchers say this discovery is important because cancer mortality is mainly due to metastatic tumors, those that grow from cells that have traveled from their original site to another part of the body. These are called secondary tumors. Only 10% of cancer deaths are caused by the primary tumors.
The scientists, from the Massachusetts Institute of Technology, say that finding a way to stop cancer cells from sticking to new sites could interfere with metastatic disease, and halt the growth of secondary tumors.
Scientists from the Physical Sciences-Oncology Centers, USA, reported in the journalScientific Reports (April 2013 issue) that malignant cells are much “nimbler” than non-malignant ones. Malignant cells can pass more easily through smaller gaps, as well as applying a much greater force on their environment compared to other cells.
Professor Robert Austin and team created a new catalogue of the physical and chemical features of cancerous cells with over 100 scientists from 20 different centers across the United States.
The authors believe their catalogue will help oncologists detect cancerous cells in patients early on, thus preventing the spread of the disease to other parts of the body.
Prof. Austin said “By bringing together different types of experimental expertise to systematically compare metastatic and non-metastatic cells, we have advanced our knowledge of how metastasis occurs.”
Cells can experience uncontrolled growth if there are mutations to DNA, and therefore, alterations to the genes involved in cell division. Four key types of gene are responsible for the cell division process: oncogenes tell cells when to divide, tumor suppressor genes tell cells when not to divide, suicide genes control apoptosis and tell the cell to kill itself if something goes wrong, and DNA-repair genes instruct a cell to repair damaged DNA.
Cancer occurs when a cell’s gene mutations make the cell unable to correct DNA damage and unable to commit suicide. Similarly, cancer is a result of mutations that inhibit oncogene and tumor suppressor gene function, leading to uncontrollable cell growth.
Carcinogens are a class of substances that are directly responsible for damaging DNA, promoting or aiding cancer. Tobacco, asbestos, arsenic, radiation such as gamma and x-rays, the sun, and compounds in car exhaust fumes are all examples of carcinogens. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. Theses free radicals damage cells and affect their ability to function normally.
Cancer can be the result of a genetic predisposition that is inherited from family members. It is possible to be born with certain genetic mutations or a fault in a gene that makes one statistically more likely to develop cancer later in life.
As we age, there is an increase in the number of possible cancer-causing mutations in our DNA. This makes age an important risk factor for cancer. Several viruses have also been linked to cancer such as: human papillomavirus (a cause of cervical cancer), hepatitis B and C (causes of liver cancer), and Epstein-Barr virus (a cause of some childhood cancers). Human immunodeficiency virus (HIV) – and anything else that suppresses or weakens the immune system – inhibits the body’s ability to fight infections and increases the chance of developing cancer.
There are five broad groups that are used to classify cancer.
Cancers are often referred to by terms that contain a prefix related to the cell type in which the cancer originated and a suffix such as -sarcoma, -carcinoma, or just -oma. Common prefixes include:
Early detection of cancer can greatly improve the odds of successful treatment and survival. Physicians use information from symptoms and several other procedures to diagnose cancer.
Imaging techniques such as X-rays, CT scans, MRI scans, PET scans, and ultrasound scansare used regularly in order to detect where a tumor is located and what organs may be affected by it. Doctors may also conduct an endoscopy, which is a procedure that uses a thin tube with a camera and light at one end, to look for abnormalities inside the body.
Extracting cancer cells and looking at them under a microscope is the only absolute way to diagnose cancer. This procedure is called a biopsy. Other types of molecular diagnostic tests are frequently employed as well. Physicians will analyze your body’s sugars, fats, proteins, and DNA at the molecular level. For example, cancerous prostate cells release a higher level of a chemical called PSA (prostate-specific antigen) into the bloodstream that can be detected by a blood test. Molecular diagnostics, biopsies, and imaging techniques are all used together to diagnose cancer.
After a diagnosis is made, doctors find out how far the cancer has spread and determine the stage of the cancer. The stage determines which choices will be available for treatment and informs prognoses. The most common cancer staging method is called the TNM system. T (1-4) indicates the size and direct extent of the primary tumor, N (0-3) indicates the degree to which the cancer has spread to nearby lymph nodes, and M (0-1) indicates whether the cancer has metastasized to other organs in the body. A small tumor that has not spread to lymph nodes or distant organs may be staged as (T1, N0, M0), for example.
TNM descriptions then lead to a simpler categorization of stages, from 0 to 4, where lower numbers indicate that the cancer has spread less. While most Stage 1 tumors are curable, most Stage 4 tumors are inoperable or untreatable.
Recent developments on cancer diagnosis
A simple blood test could be on the way to replacing the biopsy as the gold standard for detecting cancer, saving lives and money, according to researchers in the UK. In their study, carried out on known or suspected primary or secondary lung cancer who were about to undergo surgery, the blood test was accurate in predicting the presence of cancer cells in nearly 70% of cases.
Cancer symptoms are quite varied and depend on where the cancer is located, where it has spread, and how big the tumor is. Some cancers can be felt or seen through the skin – a lump on the breast or testicle can be an indicator of cancer in those locations. Skin cancer (melanoma) is often noted by a change in a wart or mole on the skin. Some oral cancers present white patches inside the mouth or white spots on the tongue.
Other cancers have symptoms that are less physically apparent. Some brain tumors tend to present symptoms early in the disease as they affect important cognitive functions. Pancreas cancers are usually too small to cause symptoms until they cause pain by pushing against nearby nerves or interfere with liver function to cause a yellowing of the skin and eyes called jaundice. Symptoms also can be created as a tumor grows and pushes against organs and blood vessels. For example, colon cancers lead to symptoms such as constipation, diarrhea, and changes in stool size. Bladder or prostate cancers cause changes in bladder function such as more frequent urination or infrequent urination.
As cancer cells use the body’s energy and interfere with normal hormone function, it is possible to present symptoms such as fever, fatigue, excessive sweating, anemia, and unexplained weight loss. However, these symptoms are common in several other maladies as well. For example, coughing and hoarseness can point to lung or throat cancer as well as several other conditions.
When cancer spreads, or metastasizes, additional symptoms can present themselves in the newly affected area. Swollen or enlarged lymph nodes are common and likely to be present when the cancer starts to spread.
If cancer spreads to the brain, patients may experience vertigo, headaches, or seizures. Spreading to the lungs may cause coughing and shortness of breath. In addition, the liver may become enlarged and cause jaundice and bones can become painful, brittle, and break easily. Symptoms of metastasis ultimately depend on the location to which the cancer has spread.
Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer begins to form. Unlike regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal cells that grows out of control.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Not all tumors are cancerous; benign tumors do not spread to other parts of the body. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements. While these symptoms may indicate cancer, they may have other causes. Over 100 cancers affect humans.
Tobacco use is the cause of about 22% of cancer deaths. Another 10% is due to obesity, poor diet, lack of physical activity and drinking alcohol. Other factors include certain infections, exposure to ionizing radiation and environmental pollutants. In the developing world nearly 20% of cancers are due to infections such as hepatitis B, hepatitis C and human papillomavirus (HPV).[ These factors act, at least partly, by changing the genes of a cell. Typically many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects from a person’s parents.Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed bybiopsy.
Many cancers can be prevented by not smoking, maintaining a healthy weight, not drinking too much alcohol, eating plenty of vegetables, fruits and whole grains, vaccination against certain infectious diseases, not eating too much processed and red meat, and avoiding too much sunlight exposure. Early detection through screening is useful for cervical and colorectal cancer. The benefits of screening in breast cancer are controv Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy, and targeted therapy. Pain and symptom management are an important part of care. Palliative care is particularly important in people with advanced disease.The chance of survival depends on the type of cancer and extent of disease at the start of treatment. In children under 15 at diagnosis the five-year survival rate in the developed world is on average 80%. For cancer in the United States the average five-year survival rate is 66%.
In 2012 about 14.1 million new cases of cancer occurred globally (not including skin cancer other than melanoma)] It caused about 8.2 million deaths or 14.6% of human deaths. The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer. If skin cancer other than melanoma were included in total new cancers each year it would account for around 40% of cases. In children, acute lymphoblastic leukaemia and brain tumors are most common except in Africa where non-Hodgkin lymphoma occurs more often. In 2012, about 165,000 children under 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age and many cancers occur more commonly in developed countries. Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world. The financial costs of cancer were estimated at $1.16 trillion US dollars per year as of 2010.
Cancers are a large family of diseases that involve abnormal cell growth with the potential to invade or spread to other parts of the body. They form a subset of neoplasms. A neoplasm or tumor is a group of cells that have undergone unregulated growth and will often form a mass or lump, but may be distributed diffusely.
All tumor cells show the six hallmarks of cancer. These characteristics are required to produce a malignant tumor. They include:
The progression from normal cells to cells that can form a detectable mass to outright cancer involves multiple steps known as malignant progression.
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancer’s type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer is a “great imitator“. Thus, it is common for people diagnosed with cancer to have been treated for other diseases, which were hypothesized to be causing their symptoms.
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in coughor pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.
General symptoms occur due to effects that are not related to direct or metastatic spread. These may include: unintentional weight loss, fever, excessive fatigue and changes to the skin. Hodgkin disease, leukemias and cancers of the liver or kidney can cause a persistent fever.
Cancer can spread from its original site by local spread, lymphatic spread to regional lymph nodes or by haematogenous spread via the blood to distant sites, known as metastasis. When cancer spreads by a haematogenous route, it usually spreads all over the body. However, cancer ‘seeds’ grow in certain selected site only (‘soil’) as hypothesized in the soil and seed hypothesis of cancer metastasis. The symptoms of metastatic cancers depend on the tumor location and can include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard), enlarged liver orenlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.
The majority of cancers, some 90–95% of cases, are due to environmental factors. The remaining 5–10% are due to inherited genetics. Environmental, as used by cancer researchers, means any cause that is not inherited genetically, such as lifestyle, economic and behavioral factors and not merely pollution. Common environmental factors that contribute to cancer death include tobacco (25–30%), diet and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity and environmental pollutants.
It is not generally possible to prove what caused a particular cancer, because the various causes do not have specific fingerprints. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional organ donors, cancer is generally not a transmissible disease.
Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.
Tobacco smoke, for example, causes 90% of lung cancer. It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus andpancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.
Tobacco is responsible about one in five cancer deaths worldwide and about one in three in the developed world 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 rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.
In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers.Cancer from work-related substance exposures may cause between 2–20% of cases, causing at least 200,000 deaths. Cancers such as as lung cancer andmesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.
Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths. In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths. A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system. More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.
Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer. Aflatoxin B1, a frequent food contaminant, causes liver cancer. Betel nut chewing can cause oral cancer. National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet while colon canceris more common in the United States. Immigrant cancer profiles develop mirror that of their new country, often within one generation.
Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion ranges from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.
Oncoviruses (viruses that can cause cancer) include human papillomavirus (cervical cancer), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi’s sarcoma herpesvirus (Kaposi’s sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma.Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).
Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation. Additionally, the majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.
Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times
Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.
Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium waveUVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.
Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources have been described as a possible carcinogen by the World Health Organization‘sInternational Agency for Research on Cancer. However, studies have not found a consistent link between mobile phone radiation and cancer risk.
The vast majority of cancers are non-hereditary (“sporadic”). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer.Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer,among others.
Some substances cause cancer primarily through their physical, rather than chemical, effects. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs. Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are believed to have similar effects. Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite and tridymite). Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.
Physical trauma resulting in cancer is relatively rare.Claims that breaking bones resulted in bone cancer, for example, have not been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer. One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. Frequent consumption of scalding hot tea may produce esophageal cancer. Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma. However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.
Chronic inflammation has been hypothesized to directly cause mutation. Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment. Oncogenes build up an inflammatory pro-tumorigenic microenvironment.
Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.
Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry and have a correspondingly higher level of prostate cancer. Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.
Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones. On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer.Osteosarcoma may be promoted by growth hormones. Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.
The affected genes are divided into two broad categories. Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.
Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. More common aremutations, which are changes in the nucleotide sequence of genomic DNA.
Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs inchronic myelogenous leukemia and results in production of the BCR–abl fusion protein, an oncogenic tyrosine kinase.
Small-scale mutations include point mutations, deletions and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the gene’s coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected cell and its descendants.
Replication of the data contained within the DNA of living cells will probabilistically result in some errors (mutations). Complex error correction and prevention is built into the process and safeguards the cell against cancer. If significant error occurs, the damaged cell can self-destruct through programmed cell death, termed apoptosis. If the error control processes fail, then the mutations will survive and be passed along to daughter cells.
Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation or hypoxia.
The errors that cause cancer are self-amplifying and compounding, for example:
The transformation of a normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the body’s design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed clonal evolution, drives progression towards more invasive stages.Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies.
Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.
The classical view of cancer is a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes and chromosomal abnormalities. Later epigenetic alterations‘ role was identified.
Epigenetic alterations refer to functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1).Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, last for multiple generations and can be considered to be epimutations (equivalent to mutations).
Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.
While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability characteristic of cancers.
Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damage remains in cells at a higher than usual level (5th level) and cause increased frequencies of mutation and/or epimutation (6th level). Mutation rates increase substantially in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR). Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.
Higher levels of DNA damage cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.
Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations). Germ line DNA repair mutations are noted on the figure’s left side. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.
In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, frequent epigenetic alterations of the DNA sequences code for small RNAs called microRNAs (or miRNAs). MiRNAs do not code for proteins, but can “target” protein-coding genes and reduce their expression.
Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see Field defects in progression to cancer). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may be “driver” mutations and the remaining ones may be “passenger” mutations.
Metastasis is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize.]Most cancer deaths are due to cancer that has metastasized.
Metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones.
Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these lead to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly includeblood tests, X-rays, CT scans and endoscopy.
People may become extremely anxious and depressed post-diagnosis. The risk of suicide in people with cancer is approximately double the normal risk.
Cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include:
Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ or tissue of origin as the root. For example, cancers of the liver parenchymaarising from malignant epithelial cells is called hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma and a cancer arising from fat cells is called aliposarcoma. For some common cancers, the English organ name is used. For example, the most common type of breast cancer is called ductal carcinoma of the breast. Here, the adjective ductal refers to the appearance of the cancer under the microscope, which suggests that it has originated in the milk ducts.
Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name of this frequently occurring benign tumor in the uterus is fibroid). Confusingly, some types of cancer use the -noma suffix, examples including melanoma and seminoma.
The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate theprognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of tissue tests. These tests may provide information about molecular changes (such as mutations, fusion genes and numerical chromosome changes) and may thus also indicate the prognosis and best treatment.
An invasive ductal carcinoma of the breast (pale area at the center) surrounded by spikes of whitish scar tissue and yellow fatty tissue
Cancer treatment depends on the type of cancer, the stage of the cancer (how much it has spread), age, health status, and additional personal characteristics. There is no single treatment for cancer, and patients often receive a combination of therapies and palliative care. Treatments usually fall into one of the following categories: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, or gene therapy.
Surgery is the oldest known treatment for cancer. If a cancer has not metastasized, it is possible to completely cure a patient by surgically removing the cancer from the body. This is often seen in the removal of the prostate or a breast or testicle. After the disease has spread, however, it is nearly impossible to remove all of the cancer cells. Surgery may also be instrumental in helping to control symptoms such as bowel obstruction or spinal cord compression.
Innovations continue to be developed to aid the surgical process, such as the iKnife that “sniffs” out cancer. Currently, when a tumor is removed surgeons also take out a “margin” of healthy tissue to make sure no malignant cells are left behind. This usually means keeping the patients under general anesthetic for an extra 30 minutes while tissue samples are tested in the lab for “clear margins”. If there are no clear margins, the surgeon has to go back in and remove more tissue (if possible). Scientists from Imperial College London say the iKnife may remove the need for sending samples to the lab.
In a study carried out at Washington University School of Medicine in 2014, researchers found a way of visualizing cancer cells using high-tech glasses designed to make it easier for surgeons to distinguish between cancerous and healthy tissue. Viewed through the glasses, cancer cells appear to glow blue under a special light, thanks to a fluorescent marker injected in the tumor that attaches only to cancerous and not to healthy cells. Also, the lighter the shade of blue, the more concentrated the cancer cells are.
Promising results of an early small trial at Duke University Medical Center in Durham, NC have suggested a new injectable agent that makes cancer cells in a tumor fluoresce, could help surgeons remove all of the cancerous tissue on the first attempt. Tests continue to be carried out.
Radiation treatment, also known as radiotherapy, destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide.
Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Early radiation treatments caused severe side-effects because the energy beams would damage normal, healthy tissue, but technologies have improved so that beams can be more accurately targeted. Radiotherapy is used as a standalone treatment to shrink a tumor or destroy cancer cells (including those associated with leukemia and lymphoma), and it is also used in combination with other cancer treatments.
Chemotherapy utilizes chemicals that interfere with the cell division process – damaging proteins or DNA – so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. It is a necessary treatment for some forms of leukemia and lymphoma. Chemotherapy treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options.
Immunotherapy aims to get the body’s immune system to fight the tumor. Local immunotherapy injects a treatment into an affected area, for example, to cause inflammation that causes a tumor to shrink. Systemic immunotherapy treats the whole body by administering an agent such as the protein interferon alpha that can shrink tumors. Immunotherapy can also be considered non-specific if it improves cancer-fighting abilities by stimulating the entire immune system, and it can be considered targeted if the treatment specifically tells the immune system to destroy cancer cells. These therapies are relatively young, but researchers have had success with treatments that introduce antibodies to the body that inhibit the growth of breast cancer cells. Bone marrow transplantation (hematopoetic stem cell transplantation) can also be considered immunotherapy because the donor’s immune cells will often attack the tumor or cancer cells that are present in the host.
Several cancers have been linked to some types of hormones, most notably breast and prostate cancer. Hormone therapy is designed to alter hormone production in the body so that cancer cells stop growing or are killed completely. Breast cancer hormone therapies often focus on reducing estrogen levels (a common drug for this is tamoxifen) and prostate cancer hormone therapies often focus on reducing testosterone levels. In addition, some leukemia and lymphoma cases can be treated with the hormone cortisone.
The goal of gene therapy is to replace damaged genes with ones that work to address a root cause of cancer: damage to DNA. For example, researchers are trying to replace the damaged gene that signals cells to stop dividing (the p53 gene) with a copy of a working gene. Other gene-based therapies focus on further damaging cancer cell DNA to the point where the cell commits suicide. Gene therapy is a very young field and has not yet resulted in any successful treatments.
Cancers that are closely linked to certain behaviors are the easiest to prevent. For example, choosing not to smoke tobacco or drink alcohol significantly lower the risk of several types of cancer – most notably lung, throat, mouth, and liver cancer. Even if you are a current tobacco user, quitting can still greatly reduce your chances of getting cancer.
Skin cancer can be prevented by staying in the shade, protecting yourself with a hat and shirt when in the sun, and using sunscreen. Diet is also an important part of cancer prevention since what we eat has been linked to the disease. Physicians recommend diets that are low in fat and rich in fresh fruits and vegetables and whole grains.
Certain vaccinations have been associated with the prevention of some cancers. For example, many women receive a vaccination for the human papillomavirus because of the virus’s relationship with cervical cancer. Hepatitis B vaccines prevent the hepatitis B virus, which can cause liver cancer.
Some cancer prevention is based on systematic screening in order to detect small irregularities or tumors as early as possible even if there are no clear symptoms present. Breast self-examination, mammograms, testicular self-examination, and Pap smears are common screening methods for various cancers.
Researchers from Northwestern University Feinberg School of Medicine in Chicago reported in the journal Circulation that the 7 steps recommended for protection against heart disease can also reduce the risk of developing cancer,. They include being physically active, eating a healthy diet, controlling cholesterol, managing blood pressure, reducing blood sugar and not smoking.
Researchers at The Institute of Cancer Research reported in the journal Nature Reviews Drug Discovery (January 2013 issue) that they have found a new way of rapidly prioritizing the best druggable targets online. They managed to identify 46 previously overlooked targets.
The researchers used the canSAR database together with a tool and were able to compare up to 500 drug targets in a matter of minutes. With this method, it is possible to analyze huge volumes of data to discover new drug targets, which can lead to the development of effective cancer medications.
The scientists analyzed 479 cancer genes to determine which ones were potential targets for medications. Their approach was effective – they found 46 new potentially “druggable” cancer proteins.
Not only will this approach lead to much more targeted cancer drugs, but also considerably cheaper ones, the authors added.
Cancer prevention is defined as active measures to decrease cancer risk.The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable. Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.
Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, insufficient diet, physical inactivity, alcohol, sexually transmitted infections andair pollution.] Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior. : Diet and cancer
While many dietary recommendations have been proposed to reduce caner risks, the evidence to support them is not definitive. The primary dietary factors that increase risk are obesity and alcoholconsumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion. A 2014 meta-analysis find no relationship between fruits and vegetables and cancer. Coffee is associated with a reduced risk of liver cancer. Studies have linked excess consumption of red or processed meat to an increased risk of breast cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures. In 2015 the IARC reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree, red meat was linked to some cancers.
Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains and fish and an avoidance of processed and red meat (beef, pork, lamb), animal fats and refined carbohydrates.
Medications can be used to prevent cancer in a few circumstances. In the general population, NSAIDs reduce the risk of colorectal cancer, however due to cardiovascular and gastrointestinal side effects they cause overall harm when used for prevention. Aspirin has been found to reduce the risk of death from cancer by about 7%. COX-2 inhibitors may decrease the rate of polyp formation in people with familial adenomatous polyposis, however it is associated with the same adverse effects as NSAIDs. Daily use of tamoxifen or raloxifene reduce the risk of breast cancer in high-risk women. The benefit versus harm for 5-alpha-reductase inhibitor such as finasteride is not clear.
Vitamins are not effective at preventing cancer,] although low blood levels of vitamin D are correlated with increased cancer risk. Whether this relationship is causal and vitamin D supplementation is protective is not determined. Beta-carotene supplementation increases lung cancer rates in those who are high risk. Folic acid supplementation is not effective in preventing colon cancer and may increase colon polyps. It is unclear if selenium supplementation has an effect.
Vaccines have been developed that prevent infection by some carcinogenic viruses. Human papillomavirus vaccine (Gardasil and Cervarix) decrease the risk of developing cervical cancer. Thehepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer. The administration of human papillomavirus and hepatitis B vaccinations is recommended when resources allow.
Unlike diagnostic efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear. This may involve physical examination, blood or urine tests or medical imaging.
Cancer screening is not available for many types of cancers. Even when tests are available, they may not be recommended for everyone. Universal screening or mass screening involves screening everyone. Selective screening identifies people who are at higher risk, such as people with a family history. Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening. These factors include:
The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers:
|BRCA1, BRCA2||Breast, ovarian, pancreatic|
|HNPCC, MLH1, MSH2, MSH6, PMS1, PMS2||Colon, uterine, small bowel, stomach, urinary tract|
Genetic testing for individuals at high-risk of certain cancers is recommended by unofficial groups. Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.
Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patient’s health and preferences. The treatment intent may or may not be curative.
Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. The term encompasses a variety of drugs, which are divided into broad categories such as alkylating agents and antimetabolites. Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells.
Targeted therapy is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML). Currently, targeted therapies exist for breast cancer,multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.
The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer,pancreatic cancer, osteogenic sarcoma, testicular cancer, ovarian cancer and certain lung cancers. Chemotherapy is curative for some cancers, such as some leukemias, ineffective in somebrain tumors, and needless in others, such as most non-melanoma skin cancers. The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.
Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve symptoms. It works by damaging the DNA of cancerous tissue, killing it. To spare normal tissues (such as skin or organs, which radiation must pass through to treat the tumor), shaped radiation beams are aimed from multiple exposure angles to intersect at the tumor, providing a much larger dose there than in the surrounding, healthy tissue. As with chemotherapy, cancers vary in their response to radiation therapy.
Radiation therapy is used in about half of cases. The radiation can be either from internal sources (brachytherapy) or external sources. The radiation is most commonly low energy x-rays for treating skin cancers, while higher energy x-rays are used for cancers within the body. Radiation is typically used in addition to surgery and or chemotherapy. For certain types of cancer, such as early head and neck cancer, it may be used alone.For painful bone metastasis, it has been found to be effective in about 70% of patients.
Surgery is the primary method of treatment for most isolated, solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of definitive diagnosis and staging of tumors, as biopsies are usually required. In localized cancer, surgery typically attempts to remove the entire mass along with, in certain cases, the lymph nodes in the area. For some types of cancer this is sufficient to eliminate the cancer.
Palliative care refers to treatment that attempts to help the patient feel better and may be combined with an attempt to treat the cancer. Palliative care includes action to reduce physical, emotional, spiritual and psycho-social distress. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve quality of life.
People at all stages of cancer treatment typically receive some kind of palliative care. In some cases, medical specialty professional organizations recommend that patients and physicians respond to cancer only with palliative care. This applies to patients who:
Palliative care may be confused with hospice and therefore only indicated when people approach end of life. Like hospice care, palliative care attempts to help the patient cope with their immediate needs and to increase comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed.
Multiple national medical guidelines recommend early palliative care for patients whose cancer has produced distressing symptoms or who need help coping with their illness. In patients first diagnosed with metastatic disease, palliative care may be immediately indicated. Palliative care is indicated for patients with a prognosis of less than 12 months of life even given aggressive treatment.
A variety of therapies using immunotherapy, stimulating or helping the immune system to fight cancer, have come into use since 1997. Approaches include antibodies, checkpoint therapy and adoptive cell transfer.
Complementary and alternative cancer treatments are a diverse group of therapies, practices and products that are not part of conventional medicine. “Complementary medicine” refers to methods and substances used along with conventional medicine, while “alternative medicine” refers to compounds used instead of conventional medicine. Most complementary and alternative medicines for cancer have not been studied or tested using conventional techniques such as clinical trials. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers stated, “The label ‘unproven’ is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been ‘disproven’.
Survival rates vary by cancer type and by the stage at which it is diagnosed, ranging from majority survival to complete mortality five years after diagnosis. Once a cancer has metastasized, prognosis normally becomes much worse.About half of patients receiving treatment for invasive cancer (excluding carcinoma in situ and non-melanoma skin cancers) die from that cancer or its treatment.
Survival is worse in the developing world, partly because the types of cancer that are most common there are harder to treat than those associated with developed countries.
Those who survive cancer develop a second primary cancer at about twice the rate of those never diagnosed. The increased risk is believed to be primarily due to the same risk factors that produced the first cancer, partly due to treatment of the first cancer and to better compliance with screening.
Predicting short- or long-term survival depends on many factors. The most important are the cancer type and the patient’s age and overall health. Those who are frail with other health problems have lower survival rates than otherwise healthy people. Centenarians are unlikely to survive for five years even if treatment is successful. People who report a higher quality of life tend to survive longer.]People with lower quality of life may be affected by depression and other complications and/or disease progression that both impairs quality and quantity of life. Additionally, patients with worse prognoses may be depressed or report poorer quality of life because they perceive that their condition is likely to be fatal.