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Abstract
The growing number of reports documenting successful immunotherapy of tumor patients and the increasing knowledge of the mechanisms governing immune reactions against tumor cells warrant further experimental efforts in this area. Currently, the most widely method of treating cancer is through: chemotherapy, radiation therapy, and surgery. However, immunotherapy represents the new age of cancer treatment. In this research we looked at several different immunotherapy strategies in order to validate the idea that immunotherapy is a viable method of cancer treatment.
Introduction
Cancer is one of the leading causes of death in the world today. Studies show that one in three people will suffer from some form of cancer in their lifetime. There are many different kinds of cancer that effect different parts of the body. Cancer is treated in various different ways. Some forms of cancer are curable, and some are not. Cancer usually comes from the formation of a tumor. Tumors form in the body when cells are produced unnecessarily. That is to say, that new cells are formed when they are not needed, and they group together to form a tumor. The tumor can be benign, which means that it is non-cancerous. If cells break away from a malignant tumor, they will enter the bloodstream, and spread throughout the body, damaging other parts of the body.
Quite often, cancer appears with no definite cause. However, there are some activities that people engage in, that increase the risk of cancer. Smoking can cause cancer of the lung, mouth, and throat. Alcohol can cause cancer of the mouth, throat and liver. Also, exposure to radiation and sunlight (or ultra-violet rays) can cause skin cancer. The exact cause of cancer still remains a mystery. Cancer can be detected early on by certain symptoms. As cancer progresses through its various stages, it will produce certain symptoms. The symptoms depend on the size and location of the cancer. In some areas, symptoms will not appear until the cancer is very large, making the cancer much more difficult to treat. The general symptoms of cancer are fever, fatigue, severe weight loss, an alteration of metabolism, blood clots, weakness and dizziness, and sores that don’t heal.
There are various different methods of treatment for cancer. Surgery is typically the first choice of most patients. If the cancer is localized, meaning it hasn’t spread, surgery is the best option. The surgeon will remove the tumor and the surrounding tissue. Surgery offers the greatest chance of a cure. The next method of treatment, which is usually a patients second choice. Is chemotherapy. This method treats cancer cells that have spread.
Definition, Signs and Symptoms
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 limp, 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:
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancers 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 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, 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. 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.
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 or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.
Causes
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.
Chemicals: 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 and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.
Tobacco is responsible for 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 lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.
Diet & Exercise: Diet, physical inactivity and obesity are related to up to 30-35% of cancer deaths. 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 over nutrition 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.
Infection: 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 lymopmas), 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 see in Helicobacter pylori-induced gastric carcinoma. Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the baldder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinesis (cholangiocarcinoma).
Radiation: Up to 10% of invasive cancers are related to radiation exposure, uncluding 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 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 developed radiation-induced leukemia as adults, radiation exposure before birth has ten times the effect.
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. Prolong exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. 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. However, studies have not found a consistent link between mobile phone radiation and cancer risk.
Heredity: 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.
Physical agents & Hormones: 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 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. Physical trauma resulting is 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 produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. 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 glucorunide, 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.
Treatment & management
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: 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 some brain 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: 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: 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 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.
Immunotherapy: 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.
Palliative care: 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:
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.
Epilogue
Prognosis: 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 of 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. Centeranians 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. Cancer patients have an increased risk of blood clots in veins. The use of heparin appears to improve survival and decrease the risk of blood clots.
Epidemiology: In 2008, approximately 12.7 million cancers were diagnose (excluding non-melanoma skin cancers and other non-invasive cancers) and in 2010 nearly 7.98 million people died. Cancers account for approximately 13% of deaths. The most common are lung cancer (1.4 million deaths), stomach cancer (740,000), liver cancer (700,000), colorectal cancer (610,000) and breast cancer (460,000). This makes invasive cancer the leading cause of death in the developed world and the second leading in the developing world. Over half of cases occur in the developing world.
Deaths from cancer were 5.8 million in 1990. Deaths have been increasing primarily due to longer lifespans and lifestyle changes in the developing world. The most significant risk factor for developing cancer is age. Although it is possible for cancer to strike at any age, most patients with invasive cancer are over 65. According to cancer researcher Robert A. Weinberg, “If we lived long enough, sooner or later we all would get cancer.” Some of the association between aging and cancer is attributed to immunosenescence, errors accumulated in DNA over a lifetime and age-related changes in the endocrine system. Aging’s effect on cancer is complicated by factors such as DNA damage and inflammation promoting it and factors such as vascular aging and endocrine changes inhibiting it.
The growing number of reports documenting successful immunotherapy of tumor patients and the increasing knowledge of the mechanisms governing immune reactions against tumor cells warrant further experimental efforts in this area. Currently, the most widely method of treating cancer is through: chemotherapy, radiation therapy, and surgery. However, immunotherapy represents the new age of cancer treatment. In this research we looked at several different immunotherapy strategies in order to validate the idea that immunotherapy is a viable method of cancer treatment.
Introduction
Cancer is one of the leading causes of death in the world today. Studies show that one in three people will suffer from some form of cancer in their lifetime. There are many different kinds of cancer that effect different parts of the body. Cancer is treated in various different ways. Some forms of cancer are curable, and some are not. Cancer usually comes from the formation of a tumor. Tumors form in the body when cells are produced unnecessarily. That is to say, that new cells are formed when they are not needed, and they group together to form a tumor. The tumor can be benign, which means that it is non-cancerous. If cells break away from a malignant tumor, they will enter the bloodstream, and spread throughout the body, damaging other parts of the body.
Quite often, cancer appears with no definite cause. However, there are some activities that people engage in, that increase the risk of cancer. Smoking can cause cancer of the lung, mouth, and throat. Alcohol can cause cancer of the mouth, throat and liver. Also, exposure to radiation and sunlight (or ultra-violet rays) can cause skin cancer. The exact cause of cancer still remains a mystery. Cancer can be detected early on by certain symptoms. As cancer progresses through its various stages, it will produce certain symptoms. The symptoms depend on the size and location of the cancer. In some areas, symptoms will not appear until the cancer is very large, making the cancer much more difficult to treat. The general symptoms of cancer are fever, fatigue, severe weight loss, an alteration of metabolism, blood clots, weakness and dizziness, and sores that don’t heal.
There are various different methods of treatment for cancer. Surgery is typically the first choice of most patients. If the cancer is localized, meaning it hasn’t spread, surgery is the best option. The surgeon will remove the tumor and the surrounding tissue. Surgery offers the greatest chance of a cure. The next method of treatment, which is usually a patients second choice. Is chemotherapy. This method treats cancer cells that have spread.
Definition, Signs and Symptoms
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 limp, 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:
- Cell growth and division absent the proper signals
- Continuous growth and division even given contrary signals
- Avoidance of programmed cell death
- Limitless number of cell divisions
- Promoting blood vessel construction
- Invasion of tissue and formation of metastases
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancers 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 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, 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. 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.
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 or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.
Causes
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.
Chemicals: 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 and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.
Tobacco is responsible for 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 lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.
Diet & Exercise: Diet, physical inactivity and obesity are related to up to 30-35% of cancer deaths. 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 over nutrition 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.
Infection: 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 lymopmas), 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 see in Helicobacter pylori-induced gastric carcinoma. Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the baldder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinesis (cholangiocarcinoma).
Radiation: Up to 10% of invasive cancers are related to radiation exposure, uncluding 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 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 developed radiation-induced leukemia as adults, radiation exposure before birth has ten times the effect.
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. Prolong exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. 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. However, studies have not found a consistent link between mobile phone radiation and cancer risk.
Heredity: 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.
Physical agents & Hormones: 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 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. Physical trauma resulting is 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 produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. 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 glucorunide, 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.
Treatment & management
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: 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 some brain 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: 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: 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 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.
Immunotherapy: 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.
Palliative care: 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:
- Display low performance status, implying limited ability to care for themselves
- Received no benefit from prior evidence-based treatments
- Are not eligible to participate in any appropriate clinical trial
- No strong evidence implies that treatment would be effective
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.
Epilogue
Prognosis: 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 of 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. Centeranians 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. Cancer patients have an increased risk of blood clots in veins. The use of heparin appears to improve survival and decrease the risk of blood clots.
Epidemiology: In 2008, approximately 12.7 million cancers were diagnose (excluding non-melanoma skin cancers and other non-invasive cancers) and in 2010 nearly 7.98 million people died. Cancers account for approximately 13% of deaths. The most common are lung cancer (1.4 million deaths), stomach cancer (740,000), liver cancer (700,000), colorectal cancer (610,000) and breast cancer (460,000). This makes invasive cancer the leading cause of death in the developed world and the second leading in the developing world. Over half of cases occur in the developing world.
Deaths from cancer were 5.8 million in 1990. Deaths have been increasing primarily due to longer lifespans and lifestyle changes in the developing world. The most significant risk factor for developing cancer is age. Although it is possible for cancer to strike at any age, most patients with invasive cancer are over 65. According to cancer researcher Robert A. Weinberg, “If we lived long enough, sooner or later we all would get cancer.” Some of the association between aging and cancer is attributed to immunosenescence, errors accumulated in DNA over a lifetime and age-related changes in the endocrine system. Aging’s effect on cancer is complicated by factors such as DNA damage and inflammation promoting it and factors such as vascular aging and endocrine changes inhibiting it.
