From Wikipedia, the free encyclopedia
Cancer i//, also known as a
malignant tumor or malignant
neoplasm, is a group of diseases involving abnormal
cell growth with the potential to invade or spread to other parts of the body.
[1][2] Not all tumors are cancerous;
benign tumors do not spread to other parts of the body.
[2] Possible
signs and symptoms include: a new lump, abnormal bleeding, a prolonged cough, unexplained
weight loss, and a change in
bowel movements, among others.
[3] While these symptoms may indicate cancer they may also occur due to other issues.
[3] There are over 100 different known cancers that affect humans.
[2]
Tobacco use is the cause of about 22% of cancer deaths.
[1] Another 10% is due to
obesity, a poor
diet,
lack of physical activity, and drinking
alcohol.
[1] Other factors include certain
infections, exposure to
ionizing radiation, and environmental pollutants.
[4] In the
developing world nearly 20% of cancers are due to infections such as
hepatitis B,
hepatitis C, and
human papillomavirus.
[1] These factors act, at least partly, by changing the
genes of a cell.
[5] Typically many such genetic changes are required before cancer develops.
[5] Approximately 5–10% of cancers are due to genetic defects inherited from a person's parents.
[6] Cancer can be detected by certain signs and symptoms or
screening tests.
[1] It is then typically further investigated by
medical imaging and confirmed by
biopsy.
[7]
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, being
vaccinated against certain infectious diseases, not eating too much red meat, and avoiding too much exposure to sunlight.
[8][9] Early detection through
screening is useful for cervical and colorectal cancer.
[10] The benefits of screening in breast cancer are controversial.
[10][11] Cancer is often treated with some combination of
radiation therapy,
surgery,
chemotherapy, and
targeted therapy.
[1][12] Pain and symptom management are an important part of care.
Palliative care is particularly important in those with advanced disease.
[1] The chance of survival depends on the type of cancer and
extent of disease at the start of treatment.
[5] In children under 15 at diagnosis the
five year survival rate in the developed world is on average 80%.
[13] For cancer in the United States the average five year survival rate is 66%.
[14]
In 2012 about 14.1 million new cases of cancer occurred globally (not including
skin cancer other than melanoma).
[5] It caused about 8.2 million deaths or 14.6% of
all human deaths.
[5][15] The most common types of cancer in males are
lung cancer,
prostate cancer,
colorectal cancer, and
stomach cancer, and in females, the most common types are
breast cancer, colorectal cancer, lung cancer, and
cervical cancer.
[5] If
skin cancer other than
melanoma were included in total new cancers each year it would account for around 40% of cases.
[16][17] In children
acute lymphoblastic leukaemia and
brain tumors are most common except in Africa where
non-Hodgkin lymphoma occurs more often.
[13]
In 2012 about 165,000 children less than 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.
[5]
Rates are increasing as
more people live to an old age and as lifestyle changes occur in the developing world.
[18] The financial costs of cancer have been estimated at $1.16 trillion
US dollars per year as of 2010.
[19]
Definitions
Cancers are a large family of diseases which involve abnormal
cell growth with the potential to invade or spread to other parts of the body.
[1][2] 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.
[20][21]
Six
characteristics of cancer have been proposed:
- self-sufficiency in growth signalling
- insensitivity to anti-growth signals
- evasion of apoptosis
- enabling of a limitless replicative potential
- induction and sustainment of angiogenesis
- activation of metastasis and invasion of tissue.[22]
The progression from normal cells to cells that can form a
discernible mass to outright cancer involves multiple steps known as
malignant progression.
[22][23]
Signs and symptoms
Symptoms of cancer
metastasis depend on the location of the tumor.
When cancer begins, it invariably produces no symptoms. Signs and symptoms only appear as the mass continues to grow or
ulcerates. The findings that result depend on the type and location of the cancer. Few symptoms are
specific, with many of them also frequently occurring in individuals who have other conditions. Cancer is the new "
great imitator".
Thus it is not uncommon for people diagnosed with cancer to have been
treated for other diseases which were assumed to be causing their
symptoms.
[24]
Local effects
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from
lung cancer can cause blockage of the
bronchus resulting in
cough or
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, resulting in changes
in bowel habits. Masses in breasts or testicles may be easily felt.
Ulceration can cause bleeding which, 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 buildup of fluid within the chest or
abdomen.
[24]
Systemic symptoms
General symptoms occur due to distant effects of the cancer that are
not related to direct or metastatic spread. These may include:
unintentional weight loss,
fever, being excessively tired, and changes to the skin.
[25] Hodgkin disease,
leukemias, and
cancers of the liver or
kidney can cause a persistent
fever of unknown origin.
[24]
Some cancers may cause specific groups of systemic symptoms, termed
paraneoplastic phenomena.
Examples include the appearance of
myasthenia gravis in
thymoma and
clubbing in
lung cancer.
[24]
Metastasis
Cancer can spread from its original site by local spread, lymphatic
spread to regional lymph nodes or by blood (haematogenous spread) 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 location of the tumor, and can include
enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard),
enlarged liver or
enlarged spleen, which can be felt in the
abdomen, pain or
fracture of affected bones, and
neurological symptoms.
[24]
Causes
The great majority of cancers, some 90–95% of cases, are due to
environmental factors. The remaining 5–10% are due to
inherited genetics.
[4] 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.
[26] 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.
[4]
It is nearly impossible to prove what caused a cancer in any
individual, because most cancers have multiple possible causes. 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, then there is a small chance that the cancer developed
because of air pollution or radiation. Excepting the rare transmissions
that occur with pregnancies and only a marginal few organ donors, cancer
is generally not a
transmissible disease.
[27]
Chemicals
Exposure to particular substances have been linked to specific types of cancer. These substances are called
carcinogens.
Tobacco smoking causes 90% of
lung cancer.
[28] It also causes cancer in the
larynx, head, neck, stomach, bladder, kidney,
esophagus and
pancreas.
[29] Tobacco smoke contains over fifty known carcinogens, including
nitrosamines and
polycyclic aromatic hydrocarbons.
[30] Tobacco is responsible for about one in three of all cancer deaths in the developed world,
[31] and about one in five worldwide.
[30] 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.
[32][33]
In Western Europe 10% of cancers in males and 3% of all cancers in
females are attributed to alcohol exposure, especially cancer of the
liver and of the digestive tract.
[34]
Cancer related to substance exposures at work is believed to represent between 2–20% of all cases.
[35] Every year, at least 200,000 people die worldwide from cancer related to their workplaces.
[36] Millions of workers run the risk of developing cancers such as
lung cancer and
mesothelioma from inhaling tobacco smoke or
asbestos fibers on the job, or
leukemia from exposure to
benzene at their workplaces.
[36]
Diet and exercise
Diet,
physical inactivity, and
obesity are related to up to 30–35% of cancer deaths.
[4][37]
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 all
cancer deaths.
[37]
Correspondingly, 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.
[38]
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.
[37] 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.
[39] Aflatoxin B1, a frequent food contaminate, causes liver cancer.
[39] Betel nut chewing causes oral cancer.
[39] The differences in dietary practices may partly explain differences in cancer incidence in different countries. For example,
gastric cancer is more common in Japan due to its high-salt diet
[40] and
colon cancer
is more common in the United States. Immigrants develop the risk of
their new country, often within one generation, suggesting a substantial
link between diet and cancer.
[41]
Infection
Worldwide approximately 18% of cancer deaths are related to
infectious diseases.
[4] This proportion varies in different regions of the world from a high of 25% in Africa to less than 10% in the developed world.
[4] Viruses are the usual infectious agents that cause cancer but
bacteria and
parasites may also have an effect.
A virus that can cause cancer is called an
oncovirus. These include
human papillomavirus (
cervical carcinoma),
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.
[42] Parasitic infections strongly associated with cancer include
Schistosoma haematobium (
squamous cell carcinoma of the bladder) and the
liver flukes,
Opisthorchis viverrini and
Clonorchis sinensis (
cholangiocarcinoma).
[43]
Radiation
Up to 10% of invasive cancers are related to radiation exposure, including both
ionizing radiation and
non-ionizing ultraviolet radiation.
[4] Additionally, the vast 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.
[44] Residential exposure to radon gas, for example, has similar cancer risks as
passive smoking.
[44]
Radiation is a more potent source of cancer when it is combined with
other cancer-causing agents, such as radon gas exposure plus smoking
tobacco.
[44]
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 the effect.
[44]
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.
[44] It is also used in some kinds of
medical imaging.
[45]
Prolonged exposure to
ultraviolet radiation from the
sun can lead to
melanoma and other skin malignancies.
[46] Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave
UVB, as the cause of most non-melanoma
skin cancers, which are the most common forms of cancer in the world.
[46]
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's
International Agency for Research on Cancer.
[47] However, studies have not found a consistent link between cell phone radiation and cancer risk.
[48]
Heredity
The vast majority of cancers are non-hereditary ("sporadic cancers").
Hereditary cancers
are primarily caused by an inherited genetic defect. Less than 0.3% of
the population are carriers of a genetic mutation which has a large
effect on cancer risk and these cause less than 3–10% of all cancer.
[49] 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,
[49] and
hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with
colorectal cancer,
[50] among others.
Physical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects on cells.
[51] A prominent example of this is prolonged exposure to
asbestos, naturally occurring mineral fibers which are a major cause of
mesothelioma, which is a cancer of the
serous membrane, usually the serous membrane surrounding the lungs.
[51] 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.
[51] Non-fibrous particulate materials that cause cancer include powdered metallic
cobalt and
nickel, and
crystalline silica (
quartz,
cristobalite, and
tridymite).
[51]
Usually, physical carcinogens must get inside the body (such as through
inhaling tiny pieces) and require years of exposure to develop cancer.
[51]
Physical trauma resulting in cancer is relatively rare.
[52] Claims that breaking bones resulted in bone cancer, for example, have never been proven.
[52] Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer, or brain cancer.
[52]
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.
[52] Frequently drinking scalding hot tea may produce esophageal cancer.
[52]
Generally, it is believed that the cancer arises, or a pre-existing
cancer is encouraged, during the process of repairing the trauma, rather
than the cancer being caused directly by the trauma.
[52]
However, repeated injuries to the same tissues might promote excessive
cell proliferation, which could then increase the odds of a cancerous
mutation.
It is controversial whether chronic
inflammation can directly cause mutation.
[52][53]
It is recognized, however, that inflammation can contribute to
proliferation, survival, angiogenesis and migration of cancer cells by
influencing the microenvironment around tumors.
[54][55] Furthermore,
oncogenes are known to build up an inflammatory pro-tumorigenic microenvironment.
[56]
Hormones
Some
hormones play a role in the development of cancer by promoting
cell proliferation.
[57]
Insulin-like growth factors
and their binding proteins play a key role in cancer cell
proliferation, differentiation and apoptosis, suggesting possible
involvement in carcinogenesis.
[58]
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.
[57] 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 why these women have higher risk of breast cancer,
even in the absence of a breast-cancer gene.
[57]
Similarly, men of African ancestry have significantly higher levels of
testosterone than men of European ancestry, and have a correspondingly
much higher level of prostate cancer.
[57] Men of Asian ancestry, with the lowest levels of testosterone-activating
androstanediol glucuronide, have the lowest levels of prostate cancer.
[57]
Other factors are also relevant: obese people have higher levels of
some hormones associated with cancer and a higher rate of those cancers.
[57] Women who take
hormone replacement therapy have a higher risk of developing cancers associated with those hormones.
[57] On the other hand, people who exercise far more than average have lower levels of these hormones, and lower risk of cancer.
[57] Osteosarcoma may be promoted by
growth hormones.
[57]
Some treatments and prevention approaches leverage this cause by
artificially reducing hormone levels, and thus discouraging
hormone-sensitive cancers.
[57]
Pathophysiology
Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.
Genetics
Cancer is fundamentally a disease of tissue growth regulation failure. In order for a normal cell to
transform into a cancer cell, the
genes which regulate cell growth and differentiation must be altered.
[59]
The affected genes are divided into two broad categories.
Oncogenes are genes which promote cell growth and reproduction.
Tumor suppressor genes
are genes which 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
many genes are required to transform a normal cell into a cancer cell.
[60]
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 are
mutations, 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 many 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 in
chronic 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 enormous amount of 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.
[61]
The errors which cause cancer are
self-amplifying and
compounding, for example:
- A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly.
- A further mutation in an oncogene might cause the cell to reproduce
more rapidly and more frequently than its normal counterparts.
- A further mutation may cause loss of a tumor suppressor gene,
disrupting the apoptosis signalling pathway and resulting in the cell
becoming immortal.
- A further mutation in signaling machinery of the cell might send error-causing signals to nearby cells.
The transformation of 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 the controls that limit normal
tissue growth. This rebellion-like scenario becomes 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.
[62]
Characteristic abilities developed by cancers are divided into a
number of categories. Six categories were originally proposed, in a 2000
article called "
The Hallmarks of Cancer" by
Douglas Hanahan and
Robert Weinberg:
evasion of apoptosis, self-sufficiency in growth signals, insensitivity
to anti-growth signals, sustained angiogenesis, limitless replicative
potential, and metastasis. Based on further work, the same authors added
two more categories in 2011: reprogramming of energy metabolism and
evasion of immune destruction.
[22][23]
Epigenetics
The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis
Classically, cancer has been viewed as a set of diseases that are
driven by progressive genetic abnormalities that include mutations in
tumor-suppressor genes and oncogenes, and chromosomal abnormalities.
However, it has become apparent that cancer is also driven by
epigenetic alterations.
[63]
Epigenetic alterations refer to functionally relevant modifications
to the genome that do not involve a change in the nucleotide sequence.
Examples of such modifications are changes in
DNA methylation (hypermethylation and hypomethylation) and
histone modification[64] and changes in chromosomal architecture (caused by inappropriate expression of proteins such as
HMGA2 or
HMGA1).
[65] Each of these epigenetic alterations serves to regulate 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, Schnekenburger and Diederich
[66]
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 large numbers of 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.
[67][68][69][70]
Reduced expression of DNA repair genes causes deficient 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 damages remain in cells at a higher than usual level (5th level from
the top in figure), and these excess damages cause increased
frequencies of mutation and/or epimutation (6th level from top of
figure). Mutation rates increase substantially in cells defective in
DNA mismatch repair[71][72] or in
homologous recombinational repair (HRR).
[73] Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.
[74]
Higher levels of DNA damage not only cause increased mutation (right
side of figure), but also cause increased epimutation. During repair of
DNA double strand breaks, or repair of other DNA damages, incompletely
cleared sites of repair can cause epigenetic gene silencing.
[75][76]
Deficient expression of DNA repair proteins due to an inherited
mutation can cause increased risk of cancer. Individuals with an
inherited impairment in any of 34 DNA repair genes (see article
DNA repair-deficiency disorder) have an increased risk of cancer, with some defects causing up to a 100% lifetime chance of cancer (e.g. p53 mutations).
[77]
Germ line DNA repair mutations are noted in a box on the left side of
the figure, with an arrow indicating their contribution to DNA repair
deficiency. However, such germline mutations (which cause highly
penetrant cancer syndromes) are the cause of only about 1 percent of
cancers.
[78]
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 from
the top. Many studies of heavy metal-induced carcinogenesis show that
such heavy metals cause reduction in expression of DNA repair enzymes,
some through epigenetic mechanisms. In some cases, DNA repair inhibition
is proposed to be a predominant mechanism in heavy metal-induced
carcinogenicity. In addition, there are frequent epigenetic alterations
of the DNA sequences coding 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 3 or 4 may be “driver”
mutations, and the remaining ones may be “passenger” mutations.
[79]
As pointed out above under genetic alterations, cancer is caused by
failure to regulate tissue growth, when the genes which regulate cell
growth and differentiation are altered. It has become clear that these
alterations are caused by both DNA sequence mutation in
oncogenes and
tumor suppressor genes
as well as by epigenetic alterations. The epigenetic deficiencies in
expression of DNA repair genes, in particular, likely cause an increased
frequency of mutations, some of which then occur in oncogenes and tumor
suppressor genes.
Metastasis
Metastasis
is the spread of cancer to other locations in the body. The new tumors
are called metastatic umors, while the original is called the primary
tumor. Almost all cancers can metastasize.
[80] Most cancer deaths are due to cancer that has spread from its primary site to other organs (metastasized).
[81]
Metastasis is very 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.
[80]
Diagnosis
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 include
blood tests,
X-rays,
CT scans and
endoscopy.
Most people are distressed to learn that they have cancer. They may become extremely anxious and depressed. The risk of
suicide in people with cancer is approximately double the normal risk.
[82]
Classification
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:
- Carcinoma: Cancers derived from epithelial
cells. This group includes many of the most common cancers,
particularly in the aged, and include nearly all those developing in the
breast, prostate, lung, pancreas, and colon.
- Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve), each of which develop from cells originating in mesenchymal cells outside the bone marrow.
- Lymphoma and leukemia: These two classes of cancer arise from hematopoietic (blood-forming)
cells that leave the marrow and tend to mature in the lymph nodes and
blood, respectively. Leukemia is the most common type of cancer in children accounting for about 30%.[83]
- Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively).
- Blastoma:
Cancers derived from immature "precursor" cells or embryonic tissue.
Blastomas are more common in children than in older adults.
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
parenchyma arising 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 a
liposarcoma. 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.
Some types of cancer are named for the size and shape of the cells under a microscope, such as
giant cell carcinoma,
spindle cell carcinoma, and
small-cell carcinoma.
Pathology
The tissue
diagnosis given by the pathologist indicates the type of cell that is proliferating, its
histological grade, genetic abnormalities, and other features of the tumor. Together, this information is useful to evaluate the
prognosis of the patient and to choose the best treatment.
Cytogenetics and
immunohistochemistry
are other types of testing that the pathologist may perform on the
tissue specimen. These tests may provide information about the molecular
changes (such as
mutations,
fusion genes, and numerical
chromosome
changes) that have happened in the cancer cells, and may thus also
indicate the future behavior of the cancer (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
-
-
-
Prevention
Cancer prevention is defined as active measures to decrease the risk of cancer.
[84]
The vast majority of cancer cases are due to environmental risk
factors, and many, but not all, of these environmental factors are
controllable lifestyle choices. Thus, cancer is considered a largely
preventable disease.
[85]
Greater than 30% of cancer deaths could be prevented by avoiding risk factors including:
tobacco,
overweight /
obesity, an insufficient diet,
physical inactivity,
alcohol,
sexually transmitted infections, and
air pollution.
[86] Not all environmental causes are controllable, such as naturally occurring
background radiation,
and other cases of cancer are caused through hereditary genetic
disorders, and thus it is not possible to prevent all cases of cancer.
Dietary
While many dietary recommendations have been proposed to reduce the
risk of cancer, the evidence to support them is not definitive.
[8][87] The primary dietary factors that increase risk are
obesity and
alcohol consumption; with a diet low in fruits and vegetables and high in red meat being implicated but not confirmed.
[88][89] A 2014 meta-analysis did not find a relationship between fruits and vegetables and cancer.
[90] Consumption of
coffee is associated with a reduced risk of
liver cancer.
[91] Studies have linked excessive consumption of red or processed meat to an increased risk of breast cancer,
colon cancer, and
pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in meats cooked at high temperatures.
[92][93]
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.
[8][87]
Medication
The concept that medications can be used to prevent cancer is
attractive, and evidence supports their use in a few defined
circumstances.
[94] In the general population,
NSAIDs reduce the risk of
colorectal cancer, however due to the cardiovascular and gastrointestinal side effects they cause overall harm when used for prevention.
[95] Aspirin has been found to reduce the risk of death from cancer by about 7%.
[96] COX-2 inhibitor may decrease the rate of
polyp formation in people with
familial adenomatous polyposis, however it is associated with the same adverse effects as NSAIDs.
[97] Daily use of
tamoxifen or
raloxifene has been demonstrated to reduce the risk of developing
breast cancer in high-risk women.
[98] The benefit versus harm for
5-alpha-reductase inhibitor such as
finasteride is not clear.
[99]
Vitamins have not been found to be effective at preventing cancer,
[100] although low blood levels of
vitamin D are correlated with increased cancer risk.
[101][102] Whether this relationship is causal and vitamin D supplementation is protective is not determined.
[103] Beta-Carotene supplementation has been found to increase
lung cancer rates in those who are high risk.
[104] Folic acid supplementation has not been found effective in preventing colon cancer and may increase colon polyps.
[105] It is unclear if selenium supplementation has an effect.
[106]
Vaccination
Vaccines have been developed that prevent infection by some
carcinogenic viruses.
[107] Human papillomavirus vaccine (
Gardasil and
Cervarix) decreases the risk of developing
cervical cancer.
[107] The
hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer.
[107] The administration of human papillomavirus and hepatitis B vaccinations is recommended when resources allow.
[108]
Screening
Unlike diagnosis efforts prompted by
symptoms and
medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear.
[109] This may involve
physical examination,
blood or
urine tests, or
medical imaging.
[109]
Cancer screening is currently not possible for many types of cancers,
and even when tests are available, they may not be recommended for
everyone.
Universal screening or
mass screening involves screening everyone.
[110] Selective screening identifies people who are known to be at higher risk of developing cancer, such as people with a family history of cancer.
[110] Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.
[109] These factors include:
- Possible harms from the screening test: for example, X-ray images involve exposure to potentially harmful ionizing radiation.
- The likelihood of the test correctly identifying cancer.
- The likelihood of cancer being present: Screening is not normally useful for rare cancers.
- Possible harms from follow-up procedures.
- Whether suitable treatment is available.
- Whether early detection improves treatment outcomes.
- Whether the cancer will ever need treatment.
- Whether the test is acceptable to the people: If a screening test is
too burdensome (for example, being extremely painful), then people will
refuse to participate.[110]
- Cost of the test.
Recommendations
The
U.S. Preventive Services Task Force (USPSTF) strongly recommends
cervical cancer screening in women who are
sexually active and have a
cervix at least until the age of 65.
[111] They recommend that Americans be screened for
colorectal cancer via
fecal occult blood testing,
sigmoidoscopy, or
colonoscopy starting at age 50 until age 75.
[112] There is insufficient evidence to recommend for or against screening for
skin cancer,
[113] oral cancer,
[114] lung cancer,
[115] or
prostate cancer in men under 75.
[116] Routine screening is not recommended for
bladder cancer,
[117] testicular cancer,
[118] ovarian cancer,
[119] pancreatic cancer,
[120] or
prostate cancer.
[121]
The USPSTF recommends
mammography for
breast cancer screening every two years for those 50–74 years old; however, they do not recommend either
breast self-examination or
clinical breast examination.
[122] A 2011
Cochrane review
came to slightly different conclusions with respect to breast cancer
screening stating that routine mammography may do more harm than good.
[123]
Japan screens for
gastric cancer using
photofluorography due to the high incidence there.
[18]
Genetic testing
Gene |
Cancer types |
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.
[108][124]
Carriers of these mutations may then undergo enhanced surveillance,
chemoprevention, or preventative surgery to reduce their subsequent
risk.
[124]
Management
Many treatment options for cancer exist, with the primary ones including
surgery,
chemotherapy,
radiation therapy,
hormonal therapy,
targeted therapy and
palliative care.
Which treatments are used depends upon the type, location, and grade of
the cancer as well as the person's health and wishes. The
treatment intent may be curative or not curative.
Chemotherapy
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 any of a large variety of different anticancer drugs, which are divided into broad categories such as
alkylating agents and
antimetabolites.
[125] Traditional chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells.
Targeted therapy
is a form of chemotherapy which target specific molecular differences
between cancer and normal cells. The first targeted therapies to be
developed 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).
[126] Currently, there are targeted therapies for
breast cancer,
multiple myeloma,
lymphoma,
prostate cancer,
melanoma and other cancers.
[127]
The efficacy of chemotherapy depends on the type of cancer and the
stage. In combination with surgery, chemotherapy has proven useful in a
number of different cancer types including:
breast cancer, colorectal cancer,
pancreatic cancer,
osteogenic sarcoma,
testicular cancer, ovarian cancer, and certain lung cancers.
[128] The overall effectiveness ranges from being curative for some cancers, such as some
leukemias,
[129][130] to being ineffective, such as in some
brain tumors,
[131] to being needless in others, like most
non-melanoma skin cancers.
[132]
The effectiveness of chemotherapy is often limited by toxicity to other
tissues in the body. Even when it is impossible for chemotherapy to
provide a permanent cure, chemotherapy may be useful to reduce symptoms
like pain or to reduce the size of an inoperable tumor in the hope that
surgery will be possible in the future.
Radiation
Radiation therapy involves the use of
ionizing radiation
in an attempt to either cure or improve the symptoms of cancer. It
works by damaging the DNA of cancerous tissue leading to cellular death.
To spare normal tissues (such as skin or organs which radiation must
pass through to treat the tumor), shaped radiation beams are aimed from
several angles of exposure to intersect at the tumor, providing a much
larger absorbed dose there than in the surrounding, healthy tissue. As
with chemotherapy, different cancers respond differently to radiation
therapy.
[133][134][135]
Radiation therapy is used in about half of all cases and the radiation can be from either internal sources in the form of
brachytherapy
or external sources. Radiation is typically used in addition to surgery
and or chemotherapy but for certain types of cancer, such as early
head and neck cancer, may be used alone. For painful
bone metastasis, it has been found to be effective in about 70% of people.
[136]
Surgery
Surgery is the primary method of treatment of most isolated solid
cancers and may play a role in palliation and prolongation of survival.
It is typically an important part of making the definitive diagnosis and
staging the tumor 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 all that is needed to eliminate the cancer.
[128]
Palliative care
Palliative care
refers to treatment which attempts to make the person feel better and
may or may not be combined with an attempt to treat the cancer.
Palliative care includes action to reduce the physical, emotional,
spiritual, and psycho-social distress experienced by people with cancer.
Unlike treatment that is aimed at directly killing cancer cells, the
primary goal of palliative care is to improve the person's
quality of life.
People at all stages of cancer treatment should have some kind of palliative care to provide comfort. In some cases,
medical specialty professional organizations recommend that people and physicians respond to cancer only with palliative care and not with cure-directed therapy.
[137] This includes:
[138]
- people with low performance status, corresponding with limited ability to care for themselves[137]
- people who received no benefit from prior evidence-based treatments[137]
- people who are not eligible to participate in any appropriate clinical trial[137]
- people for whom the physician sees no strong evidence that treatment would be effective[137]
Palliative care is often confused with
hospice and therefore only involved when people approach
end of life.
Like hospice care, palliative care attempts to help the person cope
with the immediate needs and to increase the person's comfort. Unlike
hospice care, palliative care does not require people to stop treatment
aimed at prolonging their lives or curing the cancer.
Multiple national
medical guidelines
recommend early palliative care for people whose cancer has produced
distressing symptoms (pain, shortness of breath, fatigue, nausea) or who
need help coping with their illness. In people who have metastatic
disease when first diagnosed, oncologists should consider a palliative
care consult immediately. Additionally, an oncologist should consider a
palliative care consult in any person they feel has less than 12 months
of life even if continuing aggressive treatment.
[139][140][141]
Immunotherapy
A variety of therapies using
immunotherapy, stimulating or helping the
immune system to fight cancer, have come into use since 1997, and this continues to be an area of very active research.
[142]
Alternative medicine
Complementary and alternative cancer treatments are a diverse group of health care systems, practices, and products that are not part of conventional medicine.
[143]
"Complementary medicine" refers to methods and substances used along
with conventional medicine, while "alternative medicine" refers to
compounds used instead of conventional medicine.
[144]
Most complementary and alternative medicines for cancer have not been
rigorously studied or tested. Some alternative treatments have been
investigated and shown to be ineffective but still continue to be
marketed and promoted. Cancer researcher Andrew J. Vickers has stated:
"The label 'unproven' is inappropriate for such therapies; it is time to
assert that many alternative cancer therapies have been 'disproven'."
[145]
Edzard Ernst has stated:
- "... any alternative cancer cure is bogus by definition. There will
never be an alternative cancer cure. Why? Because if something looked
halfway promising, then mainstream oncology would scrutinize it, and if
there is anything to it, it would become mainstream almost automatically
and very quickly. All curative "alternative cancer cures" are based on
false claims, are bogus, and, I would say, even criminal."[146]
Prognosis
Cancer has a reputation as a deadly disease. Taken as a whole, about
half of people receiving treatment for invasive cancer (excluding
carcinoma in situ and non-melanoma skin cancers) die from cancer or its treatment.
[18] Survival is worse in the developing world,
[18]
partly because the types of cancer that are most common there are at
present harder to treat than those associated with the lifestyle of
developed countries.
[147]
However, the survival rates vary dramatically by type of cancer, and by
the stage at which it is diagnosed, with the range running from the
great majority of people surviving to almost no one surviving as long as
five years after diagnosis. Once a cancer has metastasized or spread
beyond its original site the prognosis normally becomes much worse.
Those who survive cancer are at increased risk of developing a second
primary cancer at about twice the rate of those never diagnosed with
cancer.
[148]
The increased risk is believed to be primarily due to the same risk
factors that produced the first cancer, partly due to the treatment for
the first cancer, and potentially related to better compliance with
screening.
[148]
Predicting either short-term or long-term survival is difficult and
depends on many factors. The most important factors are the particular
kind of cancer and the patient's age and overall health. People who are
frail with many other health problems have lower survival rates than otherwise healthy people. A
centenarian
is unlikely to survive for five years even if the treatment is
successful. People who report a higher quality of life tend to survive
longer.
[149] People with lower quality of life may be affected by
major depressive disorder
and other complications from cancer treatment and/or disease
progression that both impairs their quality of life and reduces their
quantity of life. Additionally, patients with worse prognoses may be
depressed or report a lower quality of life directly because they
correctly perceive that their condition is likely to be fatal.
People with cancer, even those who are walking on their own, have an increased risk of
blood clots in veins. The use of
heparin appears improve survival and decrease the risk of blood clots.
[150]
Epidemiology
Death rate
adjusted for age for malignant cancer per 100,000 inhabitants in 2004
[151]
no data
≤ 55
55–80
80–105
105–130
130–155
155–180
|
180–205
205–230
230–255
255–280
280–305
≥ 305
|
In 2008, approximately 12.7 million cancers were
diagnosed (excluding
non-melanoma skin cancers and other non-invasive cancers),
[18] and in 2010 nearly 7.98 million people died.
[152] Cancers as a group account for approximately 13% of all deaths each year with the most common being:
lung cancer (1.4 million deaths),
stomach cancer (740,000 deaths),
liver cancer (700,000 deaths),
colorectal cancer (610,000 deaths), and
breast cancer (460,000 deaths).
[153] This makes invasive cancer the leading cause of death in the
developed world and the second leading cause of death in the
developing world.
[18] Over half of cases occur in the developing world.
[18]
Deaths from cancer were 5.8 million in 1990
[152] and rates have been increasing primarily due to an aging population and lifestyle changes in the developing world.
[18] The most significant
risk factor for developing cancer is old age.
[154]
Although it is possible for cancer to strike at any age, most people
who are diagnosed with invasive cancer are over the age of 65.
[154] According to cancer researcher
Robert A. Weinberg, "If we lived long enough, sooner or later we all would get cancer."
[155] Some of the association between aging and cancer is attributed to
immunosenescence,
[156] errors accumulated in
DNA over a lifetime,
[157] and age-related changes in the endocrine system.
[158]
The effect of aging on cancer is complicated with a number of factors
such as DNA damage and inflammation promoting it and a number of factors
such as vascular aging and endocrine changes inhibiting it.
[159]
Some slow-growing cancers are particularly common.
Autopsy studies in Europe and Asia have shown that up to 36% of people have undiagnosed and apparently harmless
thyroid cancer at the time of their deaths, and that 80% of men develop
prostate cancer by age 80.
[160][161] As these cancers did not cause the person's death, identifying them would have represented
overdiagnosis rather than useful medical care.
The three most common
childhood cancers are
leukemia (34%),
brain tumors (23%), and
lymphomas (12%).
[162] In the United States cancer affects about 1 in 285 children.
[163] Rates of childhood cancer have increased by 0.6% per year between 1975 to 2002 in the United States
[164] and by 1.1% per year between 1978 and 1997 in Europe.
[162] Death from childhood cancer have decreased by half since 1975 in the United States.
[163]
History
Engraving with two views of a Dutch woman who had a tumor removed from her neck in 1689
Cancer has existed for all of human history.
[165] The earliest written record regarding cancer is from circa 1600 BC in the Egyptian
Edwin Smith Papyrus and describes cancer of the breast.
[165] Hippocrates (ca. 460 BC – ca. 370 BC) described several kinds of cancer, referring to them with the
Greek word
καρκίνος karkinos (
crab or
crayfish).
[165]
This name comes from the appearance of the cut surface of a solid
malignant tumor, with "the veins stretched on all sides as the animal
the crab has its feet, whence it derives its name".
[166] Galen
stated that "cancer of the breast is so called because of the fancied
resemblance to a crab given by the lateral prolongations of the tumor
and the adjacent distended veins".
[167]:738 Celsus (ca. 25 BC – 50 AD) translated
karkinos into the
Latin cancer, also meaning crab and recommended surgery as treatment.
[165] Galen (2nd century AD) disagreed with the use of surgery and recommended
purgatives instead.
[165] These recommendations largely stood for 1000 years.
[165]
In the 15th, 16th and 17th centuries, it became acceptable for doctors to
dissect bodies to discover the cause of death.
[168] The German professor
Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor
Francois de la Boe Sylvius, a follower of
Descartes, believed that all disease was the outcome of chemical processes, and that acidic
lymph fluid was the cause of cancer. His contemporary
Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was
contagious.
[169]
The physician John Hill described tobacco snuff as the cause of nose cancer in 1761.
[168] This was followed by the report in 1775 by British surgeon
Percivall Pott that
chimney sweeps' carcinoma, a cancer of the
scrotum, was a common disease among
chimney sweeps.
[170]
With the widespread use of the microscope in the 18th century, it was
discovered that the 'cancer poison' spread from the primary tumor
through the lymph nodes to other sites ("
metastasis"). This view of the disease was first formulated by the English surgeon
Campbell De Morgan between 1871 and 1874.
[171]
Society and culture
Though many diseases (such as
heart failure) may have a worse prognosis than most cases of cancer, cancer is the subject of widespread fear and taboos. The
euphemism "after a long illness" is still commonly used (2012), reflecting an apparent
stigma.
[172]
This deep belief that cancer is necessarily a difficult and usually
deadly disease is reflected in the systems chosen by society to compile
cancer statistics: the most common form of cancer—non-melanoma
skin cancers, accounting for about one-third of all cancer cases worldwide, but very few deaths
[173][174]—are
excluded from cancer statistics specifically because they are easily
treated and almost always cured, often in a single, short, outpatient
procedure.
[175]
Cancer is regarded as a disease that must be "fought" to end the "civil insurrection"; a
War on Cancer
has been declared. Military metaphors are particularly common in
descriptions of cancer's human effects, and they emphasize both the
parlous state of the affected individual's health and the need for the
individual to take immediate, decisive actions himself, rather than to
delay, to ignore, or to rely entirely on others caring for him. The
military metaphors also help rationalize radical, destructive
treatments.
[176][177]
In the 1970s, a relatively popular
alternative cancer treatment was a specialized form of
talk therapy, based on the idea that cancer was caused by a bad attitude.
[178]
People with a "cancer personality"—depressed, repressed, self-loathing,
and afraid to express their emotions—were believed to have manifested
cancer through subconscious desire. Some psychotherapists said that
treatment to change the patient's outlook on life would cure the cancer.
[178] Among other effects, this belief allows society to
blame the victim
for having caused the cancer (by "wanting" it) or having prevented its
cure (by not becoming a sufficiently happy, fearless, and loving
person).
[179]
It also increases patients' anxiety, as they incorrectly believe that
natural emotions of sadness, anger or fear shorten their lives.
[179] The idea was excoriated by the notoriously outspoken
Susan Sontag, who published
Illness as Metaphor while recovering from treatment for
breast cancer in 1978.
[178]
Although the original idea is now generally regarded as nonsense, the
idea partly persists in a reduced form with a widespread, but incorrect,
belief that deliberately cultivating a habit of
positive thinking will increase survival.
[179] This notion is particularly strong in
breast cancer culture.
[179]
One idea about why people with cancer are blamed or stigmatized, called the
just-world hypothesis,
is that blaming cancer on the patient's actions or attitudes allows the
blamers to regain a sense of control. This is based upon the blamers'
belief that the world is fundamentally just, and so any dangerous
illness, like cancer, must be a type of punishment for bad choices,
because in a just world, bad things would not happen to good people.
[180]
In 2007, the overall costs of cancer in the U.S. — including
treatment and indirect mortality expenses (such as lost productivity in
the workplace) — was estimated to be $226.8 billion. In 2009, 32% of
Hispanics and 10% of children 17 years old or younger lacked health
insurance; "uninsured patients and those from ethnic minorities are
substantially more likely to be diagnosed with cancer at a later stage,
when treatment can be more extensive and more costly."
[181]
Research
Because cancer is a class of diseases,
[182][183] it is unlikely that there will ever be a single "
cure for cancer" any more than there will be a single treatment for all
infectious diseases.
[184] Angiogenesis inhibitors were once thought to have potential as a "
silver bullet" treatment applicable to many types of cancer, but this has not been the case in practice.
[185]
It is more likely that angiogenesis inhibitors and other cancer
therapeutics will be used in combination to reduce cancer morbidity and
mortality.
[186]
Experimental cancer treatments are treatments that are being studied to see whether they work. Typically, these are studied in
clinical trials
to compare the proposed treatment to the best existing treatment. They
may be entirely new treatments, or they may be treatments that have been
used successfully in one type of cancer, and are now being tested to
see whether they are effective in another type.
[187]
More and more, such treatments are being developed alongside companion
diagnostic tests to target the right drugs to the right patients, based
on their individual biology.
[188]
Cancer research is the intense scientific effort to understand disease processes and discover possible therapies.
Research about cancer causes focuses on the following issues:
- Agents (e.g. viruses) and events (e.g. mutations) which cause or facilitate genetic changes in cells destined to become cancer.
- The precise nature of the genetic damage, and the genes which are affected by it.
- The consequences of those genetic changes on the biology of the
cell, both in generating the defining properties of a cancer cell, and
in facilitating additional genetic events which lead to further
progression of the cancer.
The improved understanding of
molecular biology and
cellular biology due to cancer research has led to a number of new treatments for cancer since U.S. President Nixon declared the "
War on Cancer"
in 1971. Since then, the U.S. has spent over $200 billion on cancer
research, including resources from the public and private sectors and
foundations.
[189]
During that time, the country has seen a five percent decrease in the
cancer death rate (adjusting for size and age of the population) between
1950 and 2005.
[190]
Hypercompetition for the financial resources that are required to
conduct science appears to suppress the creativity, cooperation,
risk-taking, and original thinking required to make fundamental
discoveries, unduly favoring low-risk research into small incremental
advancements over innovative research that might discover radically new
and dramatically improved therapy. Other consequences of the highly
pressured competition for research resources appear to be a substantial
number of research publications whose results cannot be replicated, and
perverse incentives in research funding that encourage grantee
institutions to grow without making sufficient investments in their own
faculty and facilities.
[191][192][193][194]
Pregnancy
Because cancer is largely a disease of older adults, it is not common
in pregnant women. Cancer affects approximately 1 in 1,000 pregnant
women.
[195]
The most common cancers found during pregnancy are the same as the most
common cancers found in non-pregnant women during childbearing ages:
breast cancer, cervical cancer, leukemia, lymphoma, melanoma, ovarian
cancer, and colorectal cancer.
[195]
Diagnosing a new cancer in a pregnant woman is difficult, in part
because any symptoms are commonly assumed to be a normal discomfort
associated with pregnancy.
[195]
As a result, cancer is typically discovered at a somewhat later stage
than average in many pregnant or recently pregnant women. Some imaging
procedures, such as
MRIs (magnetic resonance imaging),
CT scans, ultrasounds, and
mammograms with fetal shielding are considered safe during pregnancy; some others, such as
PET scans are not.
[195]
Treatment is generally the same as for non-pregnant women.
[195]
However, radiation and radioactive drugs are normally avoided during
pregnancy, especially if the fetal dose might exceed 100 cGy. In some
cases, some or all treatments are postponed until after birth if the
cancer is diagnosed late in the pregnancy. Early deliveries to speed the
start of treatment are not uncommon. Surgery is generally safe, but
pelvic surgeries during the first trimester may cause miscarriage. Some
treatments, especially certain chemotherapy drugs given during the
first trimester, increase the risk of
birth defects and
pregnancy loss (spontaneous abortions and stillbirths).
[195]
Elective
abortions
are not required and, for the most common forms and stages of cancer,
do not improve the likelihood of the mother surviving or being cured.
[195]
In a few instances, such as advanced uterine cancer, the pregnancy
cannot be continued, and in others, such as an acute leukemia discovered
early in pregnancy, the pregnant woman may choose to have an abortion
so that she can begin aggressive chemotherapy without worrying about
birth defects.
[195]
Some treatments may interfere with the mother's ability to give birth vaginally or to breastfeed her baby.
[195]
Cervical cancer may require birth by Caesarean section. Radiation to
the breast reduces the ability of that breast to produce milk and
increases the risk of
mastitis.
Also, when chemotherapy is being given after birth, many of the drugs
pass through breast milk to the baby, which could harm the baby.
[195]
Other animals
Veterinary oncology,
concentrating mainly on cats and dogs, is a growing specialty in
wealthy countries, and the major forms of human treatment such as
surgery and radiotherapy may be offered. The most common types of cancer
differ, but the cancer burden seems at least as high in pets as in
humans. Animals, typically rodents, are often used in cancer research,
and studies of natural cancers in larger animals may benefit research
into human cancer.
[196]
In non-humans, a few types of
transmissible cancer
have been described, wherein the cancer spreads between animals by
transmission of the tumor cells themselves. This phenomenon is seen in
dogs with
Sticker's sarcoma, also known as canine transmissible venereal tumor,
[197] as well as
devil facial tumor disease in
Tasmanian devils.