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History of Cancer

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Buckwirth
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Over several posts, I'm going to repost each of the chapters from cancer.com

Hope you all enjoy the read. I learned some new things, maybe you will too!

:-)

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Buckwirth
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Renaissance period
During the Renaissance, beginning in the 15th century, scientists in Italy developed a greater understanding of the human body. Scientists like Galileo and Newton began to use the scientific method, which later was used to study disease. Autopsies, done by Harvey (1628), allowed an understanding of the circulation of blood through the heart and body that had until then been a mystery.

In 1761, Giovanni Morgagni of Padua was the first to do something which has become routine today -- he did autopsies to relate the patient's illness to the pathologic findings after death. This laid the foundation for scientific oncology, the study of cancer.

The famous Scottish surgeon John Hunter (1728–1793) suggested that some cancers might be cured by surgery and described how the surgeon might decide which cancers to operate on. If the tumor had not invaded nearby tissue and was "moveable," he said, "There is no impropriety in removing it."

A century later the development of anesthesia allowed surgery to flourish and the classic cancer operations such as radical mastectomy were developed.

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Nineteenth century
The 19th century saw the birth of scientific oncology with use of the modern microscope in studying diseased tissues. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer. As Morgagni had linked autopsy findings seen with the unaided eye with the clinical course of illness, so Virchow correlated the microscopic pathology.

This method not only allowed a better understanding of the damage cancer had done, but also laid the foundation for the development of cancer surgery. Body tissues removed by the surgeon could now be examined and a precise diagnosis made. The pathologist could also tell the surgeon whether the operation had completely removed the cancer.

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Cancer causes: Theories throughout history
From the earliest times, physicians have puzzled over the causes of cancer. The Egyptians blamed cancers on the gods.

Humoral theory: Hippocrates believed that the body had 4 humors (body fluids) -- blood, phlegm, yellow bile, and black bile. When the humors were balanced, a person was healthy. Too much or too little of any of them caused disease. An excess of black bile in various body sites was thought to cause cancer. This theory of cancer was passed on by the Romans and was embraced by the influential doctor Galen’s medical teaching, which remained the unchallenged standard through the Middle Ages for over 1300 years. During this period, the study of the body, including autopsies, was prohibited for religious reasons, thus limiting knowledge.

Lymph theory: Among theories that replaced the humoral theory of cancer was cancer's formation by another fluid, lymph. Life was believed to consist of continuous and appropriate movement of the fluid parts through solids. Of all the fluids, the most important were blood and lymph. Stahl and Hoffman theorized that cancer was composed of fermenting and degenerating lymph varying in density, acidity, and alkalinity. The lymph theory gained rapid support. The eminent surgeon John Hunter (1723–1792) agreed that tumors grow from lymph constantly thrown out by the blood.

Blastema theory: In 1838, German pathologist Johannes Muller demonstrated that cancer is made up of cells and not lymph, but he believed that cancer cells did not arise from normal cells. Muller proposed that cancer cells arose from budding elements (blastema) between normal tissues. His student, Rudolph Virchow (1821–1902), the famous German pathologist, determined that all cells, including cancer cells, are derived from other cells.

Chronic irritation theory: Virchow proposed that chronic irritation was the cause of cancer, but he falsely believed that cancers "spread like a liquid." A German surgeon, Karl Thiersch, showed that cancers metastasize through the spread of malignant cells and not through some unidentified fluid.

Trauma theory: Despite advances in the understanding of cancer, from the late 1800s until the 1920s, trauma was thought by some to cause cancer. This belief was maintained despite the failure of injury to cause cancer in experimental animals.

Parasite theory: In the 17th and 18th centuries, some believed that cancer was contagious. In fact, the first cancer hospital in France was forced to move from the city in 1779 because of the fear of the spread of cancer throughout the city. Although human cancer, itself, is not contagious, we now know that certain viruses, bacteria, and parasites can increase a person's risk of developing cancer.

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Modern knowledge and cancer cause
By the middle of the 20th century, scientists had in their hands the instruments needed to begin solving the complex problems of chemistry and biology. James Watson and Francis Crick, who received a Nobel Prize in 1962 for their work, had discovered the exact chemical structure of DNA, the basic material in genes.

DNA was found to be the basis of the genetic code that gives orders to all cells. After learning how to translate this code, scientists were able to understand how genes worked and how they could be damaged by mutations (changes or mistakes in genes). These modern techniques of chemistry and biology answered many complex questions about cancer.

Scientists already knew that cancer could be caused by chemicals, radiation, and viruses, and that sometimes cancer seemed to run in families. But as the understanding of DNA and genes increased, they learned that it was the damage to DNA by chemicals and radiation, or the introduction of new DNA sequences by viruses that often led to the development of cancer. It became possible to pinpoint the exact site of the damage to a specific gene.

Scientists discovered that sometimes defective genes are inherited, and sometimes these inherited genes are defective at the same points that chemicals exerted their effect. In other words, most of the things that caused cancer (carcinogens) caused genetic damage (mutations), these mutations led to abnormal groups of cells (called clones), the mutant clones evolved to even more malignant clones over time, and the cancer progressed by more and more genetic damage and mutations. Normal cells with damaged DNA die; cancer cells with damaged DNA do not. The discovery of this critical difference answered many questions that have troubled scientists for many years.

During the 1970s, scientists discovered 2 important families of genes: oncogenes and tumor suppressor genes.

Oncogenes are mutated forms of genes that cause normal cells to grow out of control and become cancer cells. They are mutations of certain normal genes of the cell called proto-oncogenes. Proto-oncogenes are the genes that normally control how often a cell divides and the degree to which it differentiates (or specializes).

Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, and tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.

It may be helpful to think of a cell as a car. For it to work properly, there need to be ways to control how fast it goes. A proto-oncogene normally functions in a way that is similar to a gas pedal -- it helps the cell grow and divide. An oncogene could be compared to a gas pedal that is stuck down, which causes the cell to divide out of control. A tumor suppressor gene is like the brake pedal on a car. It normally keeps the cell from dividing too quickly just as a brake keeps a car from going too fast. When something goes wrong with the gene, such as a mutation, cell division can get out of control.

Slowly, medical scientists are identifying the oncogenes and tumor suppressor genes that are damaged by chemicals or radiation and the genes that, when inherited, can lead to cancer. For example, the discovery during the 1990s of 2 genes that cause some breast cancers, BRCA1 and BRCA2, represents considerable promise because these genes can be used to identify people who have a higher probability of developing breast cancer.

Other genes have been discovered that are associated with some cancers that run in families, such as cancers of the colon, rectum, kidney, ovary, thyroid, pancreas, and skin melanoma. Familial cancer is not nearly as common as spontaneous cancer. It is less than 15% of all cancers. Still, it is important to understand these cancers because with continued research in genetics we may be able to identify people at very high risk.

Once researchers recognized the importance of specific genetic changes in cancer, they soon began working to develop targeted therapies (drugs or substances that interfere with specific molecules) to overcome the effects of these changes in tumor suppressor genes and especially in oncogenes.

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Viral and chemical carcinogens
In 1915 cancer was induced in lab animals for the first time by a chemical, coal tar, applied to rabbit skin at Tokyo University by Katsusaburo Yamagiwa and Koichi Ichikawa. One hundred and fifty years had passed since clinician John Hill of London recognized tobacco as a carcinogen (a substance known or believed to cause cancer in humans). Many more years passed before tobacco was "rediscovered" as the most destructive source of chemical carcinogens known to man.

Today we recognize and avoid many specific substances that cause cancer: coal tars and their derivatives (like benzene), some hydrocarbons, aniline (a substance used to make dyes), asbestos, and others. Radiation from a variety of sources, including the sun, is known to cause cancer. To ensure the public's safety, the government has set standards for many substances, including benzene, asbestos, hydrocarbons in the air, arsenic in drinking water, and radiation.

In 1911, Peyton Rous at the Rockefeller Institute in New York, described a type of cancer (sarcoma) in chickens caused by what later became known as the Rous sarcoma virus. He was awarded the Nobel Prize for that work in 1968. Several viruses are now linked to cancer in humans, too:

Long-standing liver infection with the hepatitis B or C viruses can lead to cancer of the liver.
A variety of the herpes virus, the Epstein-Barr virus, causes infectious mononucleosis and has been linked to non-Hodgkin lymphomas and nasopharyngeal cancer.
The human immunodeficiency virus (HIV) is associated with an increased risk of developing several cancers, especially Kaposi sarcoma and non-Hodgkin lymphoma.
Human papilloma viruses (HPVs) have been linked to many cancers, especially those of the cervix, vulva, vagina, and penis. Some head and neck cancers (mostly the tongue and tonsils) may be related to the high-risk types of HPV, too. A test for HPV types linked to cervical cancer was approved by the FDA for clinical use in cervical cancer screening in 2003. The first vaccine (Gardasil®) to prevent infection with 2 cancer-associated HPV types was approved by the FDA in 2006 for cancer prevention. A second vaccine (Cervarix®) was approved in 2009.
As of 2010, the World Health Organization's International Agency for Research on Cancer (IARC) has identified more than 100 chemical, physical, and biological carcinogens. Many of these associations were recognized long before scientists understood much about how cancer develops. Today, ongoing research is discovering new carcinogens, explaining how they cause cancer, and providing insight into ways to prevent cancer.

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Cancer epidemiology
During the 18th century, 3 important observations were made that launched the field of cancer epidemiology (the study of causes, distribution, and control of diseases).

In 1713, Bernardino Ramazzini, an Italian doctor, reported the virtual absence of cervical cancer and relatively high incidence of breast cancer in nuns and wondered if this was in some way related to their celibate lifestyle. This observation was an important step toward identifying and understanding the importance of hormones (like the changes that come with pregnancy) and sexually-transmitted infections and cancer risk.
In 1775, Percival Pott of Saint Bartholomew's Hospital in London described an occupational cancer in chimney sweeps, cancer of the scrotum, which was caused by soot collecting under the scrotum. This research led to many more studies that identified a number of occupational carcinogenic exposures and led to public health measures to reduce a person's cancer risk at work.
John Hill of London was the first to recognize the dangers of tobacco. In 1761, only a few decades after tobacco became popular in London, he wrote a book entitled Cautions Against the Immoderate Use of Snuff.
Results of epidemiologic research published during the 1950s and early 1960s showed that smoking is a cause of lung cancer, and led to the US Surgeon General's 1964 report Smoking and Health.
Epidemiologists continue their search for factors that cause cancer (like tobacco use, obesity, ultraviolet radiation) as well as those offering protection against cancer (such as physical activity and a healthy diet). This research provides evidence to guide public health recommendations and regulations. As molecular biologists learn more about how factors cause or prevent cancer, this information is used in studies of molecular epidemiology, which study the interactions between genes and external factors.

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Cancer screening and early detection
Screening refers to tests and exams used to find a disease, such as cancer, in people who do not have any symptoms. The first screening test to be widely used for cancer was the Pap test. The test was developed by George Papanicolaou as a research method in understanding the menstrual cycle. Papanicolaou soon recognized its potential for detecting cervical cancer early and presented his findings in 1923. At first, most doctors were skeptical, and it was not until the American Cancer Society promoted the test during the early 1960s that this test was widely used. Since that time, the cervical cancer death rate in the United States has declined by about 70%.

Modern mammography methods were developed late in the 1960s and first officially recommended by the ACS in 1976.

Current American Cancer Society guidelines include methods for early detection of cancers of the cervix, breast, colon and rectum, endometrium, and prostate, as well as a cancer-related check-up which, depending on a person's age and gender, might include exams for cancers of the thyroid, oral cavity, skin, lymph nodes, testes, and ovaries.

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Cancer treatments: Surgery
Ancient physicians and surgeons knew that cancer would usually come back after it was removed by surgery. The Roman physician Celsus wrote, "After excision, even when a scar has formed, none the less the disease has returned."

Galen was a 2nd-century Roman doctor whose books were preserved for centuries and who was thought to be the highest medical authority for over a thousand years. Galen viewed cancer much as Hippocrates had, and his views set the pattern for cancer management for centuries: he considered the patient incurable after a diagnosis of cancer had been made.

Even though medicine progressed and flourished in some ancient civilizations, there was little progress in cancer treatment. The approach to cancer was Hippocratic (or Galenic) for the most part. To some extent this view that cancer cannot be cured has persisted even into the 20th century. This has served to fuel the fear people have of the disease. Some people, even today, consider all cancer incurable and put off seeing a doctor until it is too late for optimal treatment.

Cancer treatment has gone through a slow process of development. The ancients recognized that there was no curative treatment once a cancer had spread and that intervention might be more harmful than no treatment at all. Galen did write about surgical cures for breast cancer if the tumor could be completely removed at an early stage. Surgery then was very primitive with many complications, including blood loss. It wasn't until the 19th and early 20th centuries that major advances were made in general surgery and cancer surgery.

There were great surgeons before the discovery of anesthesia. John Hunter, Astley Cooper, and John Warren achieved lasting acclaim for their swift and precise surgery. But when anesthesia became available in 1846, great surgeons emerged whose work so rapidly advanced the art that the next hundred years became known as "the century of the surgeon."

Three surgeons stand out because of their contributions to the art and science of cancer surgery: Bilroth in Germany, Handley in London, and Halsted in Baltimore. Their work led to "cancer operations" designed to remove all of the tumor along with the lymph nodes in the region where the tumor was located.

William Stewart Halsted, professor of surgery at Johns Hopkins University, developed the radical mastectomy during the last decade of the 19th century. His work was based in part on that of W. Sampson Handley, the London surgeon who believed that cancer spread outward by invasion from the original growth.

Halsted did not believe that cancers usually spread through the bloodstream: "Although it undoubtedly occurs, I am not sure that I have observed from breast cancer, metastasis which seemed definitely to have been conveyed by way of the blood vessels." He believed that adequate local removal of the cancer would cure it -- if the cancer later appeared elsewhere, it was a new process. That belief led him to develop the radical mastectomy for breast cancer. This became the basis of cancer surgery for almost a century until the 1970s, when modern clinical trials demonstrated that less extensive surgery is equally effective for most women with breast cancer. Today, a radical mastectomy is almost never done and the "modified radical mastectomy" is performed less frequently than before; most women with breast cancer undergo local removal of the primary tumor (lumpectomy) coupled with radiation therapy.

At the same time Halsted and Handley were developing their radical operations, another surgeon was asking, "What is it that decides which organs shall suffer in a case of disseminated cancer?" Stephen Paget, an English surgeon, concluded that cancer cells spread by way of the bloodstream to all organs in the body but were able to grow only in a few organs. In a brilliant leap of logic he drew an analogy between cancer metastasis and seeds that "are carried in all directions, but they can only live and grow if they fall on congenial soil."

Paget's conclusion that cells from a primary tumor spread through the bloodstream but could grow only in certain, and not all, organs was an accurate and highly sophisticated hypothesis that was confirmed by the techniques of modern cellular and molecular biology almost a hundred years later. This understanding of metastasis became a key element in recognizing the limitations of cancer surgery. It eventually allowed doctors to develop systemic treatments used after surgery to destroy cells that had spread throughout the body and to use less mutilating operations, for example, in treating many types of cancer. Today these systemic treatments may also be used before surgery.

During the final decades of the 20th century, surgeons developed greater technical expertise in minimizing the amounts of normal tissue removed during cancer operations. Like the trend from radical mastectomy to lumpectomy, progress was also made in removing bone and soft tissue tumors of the arms and legs without the need for amputation in most cases, and in avoiding a colostomy for most patients with rectal cancer. This progress depended not only on understanding cancer better as a disease and on better surgical instruments, but also on combining surgery with chemotherapy and/or radiation.

Until the end of the 20th century, diagnosing cancer required "exploratory surgery" to open the abdomen (belly) or chest so the surgeon could take tissue samples to be tested for cancer. Starting in the 1970s, progress in ultrasound (sonography), computed tomography (CT scans), magnetic resonance imaging (MRI scans), and positron emission tomography (PET scans) have replaced most exploratory operations. CT scans and ultrasound can be used to guide biopsy needles into tumors.

Instruments that use fiberoptic technology and miniature video cameras let doctors look inside the body. Surgeons can use special surgical instruments operated through tubes put into the body. Endoscopic surgery can remove tumors through tubes put through body openings to reach the colon, esophagus, or bladder. Similar instruments can also be put through small cuts in the skin to look and work inside the abdomen (laparoscopic surgery) or chest (thorascopic surgery).

Less invasive ways of destroying tumors without removing them are being studied and/or used. Cryosurgery (also called cryotherapy or cryoablation) uses liquid nitrogen spray or a very cold probe to freeze and kill abnormal cells. Lasers can be used to cut through tissue (instead of using a scalpel) or to vaporize (burn and destroy) cancers of the cervix, larynx (voice box), liver, rectum, skin and other organs. Radiofrequency ablation transmits radio waves to a small antenna placed in the tumor to kill cancer cells by heating them.

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Cancer treatments: Hormone therapy
Another 19th century discovery laid the groundwork for an important modern method to treat and prevent breast cancer. Thomas Beatson graduated from the University of Edinburgh in 1874 and developed an interest in the relation of the ovaries to milk formation in the breasts, probably because he grew up near a large sheep farm in rural Scotland. In 1878 he discovered that the breasts of rabbits stopped producing milk after he removed the ovaries. He described his results to the Edinburgh Medico-Chirurgical Society in 1896: "This fact seemed to me of great interest, for it pointed to one organ holding control over the secretion of another and separate organ."

Because the breast was "held in control" by the ovaries, Beatson decided to test removal of the ovaries (oophorectomy) in advanced breast cancer. He found that oophorectomy often resulted in improvement for breast cancer patients. He also suspected that "the ovaries may be the exciting cause of carcinoma" of the breast. He had discovered the stimulating effect of the female ovarian hormone (estrogen) on breast cancer, even before the hormone itself was discovered. His work provided a foundation for the modern use of hormone therapy, such as tamoxifen, to treat and prevent breast cancer.

A half century after Beatson’s discovery, a urologist at the University of Chicago, Charles Huggins, reported dramatic regression of metastatic prostate cancer after the testicles were removed. Later, drugs that blocked male hormone were found to be effective treatment for prostate cancer. Today these drugs are being studied to determine if they have a role in preventing prostate cancer.

New classes of drugs (such as aromatase inhibitors, LHRH [luteinizing hormone-releasing hormone] analogs and inhibitors, and others) have greatly changed the way prostate and breast cancers are treated. Research to better understand how hormones influence cancer growth has guided progress in developing and prescribing new drugs for cancer treatment. It is also helping researchers look at new ways to use drugs to reduce the risk of developing breast and prostate cancer.

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Cancer treatments: Radiation
As the 19th century was drawing to a close, in 1896 a German physics professor, Wilhelm Conrad Roentgen, presented a remarkable lecture entitled "Concerning a New Kind of Ray." Roentgen called it the "X-ray", with "X" being the algebraic symbol for an unknown quantity. There was immediate worldwide excitement. Within months, systems were being devised to use X-rays for diagnosis, and within 3 years radiation was used in to treat cancer.

In 1901 Roentgen received the first Nobel Prize awarded in physics. Radiation therapy began with radium and with relatively low-voltage diagnostic machines. In France a major breakthrough took place when it was discovered that daily doses of radiation over several weeks would greatly improve the patient's chance for a cure . The methods and the machines for delivery of radiation therapy have steadily improved. Today, radiation is delivered with great precision to destroy malignant tumors while limiting damage to nearby normal tissues.

At the beginning of the 20th century, shortly after radiation began to be used for diagnosis and therapy, it was discovered that radiation could cause cancer as well as cure it. Many early radiologists used the skin of their arms to test the strength of radiation from their radiotherapy machines, looking for a dose that would produce a pink reaction (erythema) that looked like sunburn. They called this the "erythema dose," and this was considered an estimate of the proper daily fraction of radiation. In retrospect, it is no surprise that many developed leukemia.

Advances in radiation physics and computer technology during the last quarter of the 20th century made it possible to aim radiation more precisely. Conformal radiation therapy (CRT) uses CT images and special computers to very precisely map the location of a cancer in 3 dimensions. The patient is fitted with a plastic mold or cast to keep the body part still. The radiation beams are matched to the shape of the tumor and delivered to the tumor from several directions. Intensity-modulated radiation therapy, is like CRT but along with aiming photon beams from several directions, the intensity (strength) of the beams can be adjusted. This gives even more control over decreasing the radiation reaching normal tissue while delivering a higher dose to the cancer.

A related technique, conformal proton beam radiation therapy, uses a similar approach to focusing radiation on the cancer. But instead of using x-rays, this technique uses proton beams. Protons are parts of atoms that cause little damage to tissues they pass through but are very effective in killing cells at the end of their path. This means that proton beam radiation can deliver more radiation to the cancer while reducing damage to nearby normal tissues.

Stereotactic radiosurgery and stereotactic radiation therapy are terms that describe several techniques used to deliver a large, precise radiation dose to a small tumor. The term surgery may be confusing because no cut (incision) is actually made. The most common site being treated with this technique is the brain. The linear accelerator, or a special machine known as a Gamma Knife, can be used to deliver this treatment. Research is being done to produce delivery systems to treat sites other than the brain.

Intraoperative radiation therapy (IORT) is a form of treatment that delivers radiation at the time of surgery. The radiation can be given directly to the cancer or to the adjacent tissues after the cancer has been removed. It is more commonly used in abdominal or pelvic cancers and in cancers that tend to recur (return after treatment). IORT minimizes the amount of tissue that is exposed to radiation because normal tissues can be moved out of the way during surgery and shielded, allowing a higher dose of radiation to the cancer.

Chemical modifiers or radiosensitizers are substances that make cancer more sensitive to radiation. The goal of research into these types of substances is to develop agents that will make the tumor more sensitive without affecting normal tissues. Research is also looking for substances that may protect normal cells from radiation.

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Cancer treatments: Chemotherapy
During World War II, naval personnel who were exposed to mustard gas as a result of a military action were found to have toxic effects on the bone marrow cells that develop into blood cells. During that same period, the US Army was studying a number of chemicals related to mustard gas in order to develop more effective agents and develop protective measures. In the course of that work, a compound called nitrogen mustard was studied and found to work against a cancer of the lymph nodes called lymphoma. This agent served as the model for a long series of similar but more effective agents (called alkylating agents) that killed rapidly growing cancer cells by damaging their DNA.

Not long after the discovery of nitrogen mustard, Sidney Farber of Boston demonstrated that aminopterin, a compound related to the vitamin, folic acid, produced remission in children with acute leukemia. Aminopterin blocked a critical chemical reaction needed for DNA replication. That drug was the predecessor of methotrexate, a cancer treatment drug used commonly today. Since then, other researchers discovered drugs that blocked different functions involved in cell growth and replication. The era of chemotherapy had begun. Metastatic cancer was first cured in 1956 when methotrexate was used to treat a rare tumor called choriocarcinoma.

Over the years, the development and use of chemotherapy drugs (chemo) have resulted in the successful treatment of many people with cancer. Long-term remissions and even cures of many patients with Hodgkin disease and childhood ALL (acute lymphoblastic leukemia) with chemo were first reported during the 1960s. Cures of testicular cancer were seen during the next decade. Many other cancers can be controlled with chemo for long periods of time, even if they are not cured. Today, several approaches are being studied to improve the activity and reduce the side effects of chemotherapy. These include:

New drugs, new combinations of drugs, and new delivery techniques
Novel approaches to targeting drugs more specifically at the cancer cells (such as liposomal therapy and monoclonal antibody therapy) to produce fewer side effects
Drugs to reduce side effects, like colony-stimulating factors, chemoprotective agents (such as dexrazoxane and amifostine), and anti-emetics (to reduce nausea and vomiting)
Agents that overcome multi-drug resistance
Liposomal therapy is a new technique that puts chemo drugs inside liposomes (synthetic fat globules). The liposome, or fatty coating, helps them penetrate the cancer cells more selectively and decreases possible side effects (like hair loss, nausea, and vomiting). Examples of liposomal drugs are Doxil (the encapsulated form of doxorubicin) and Daunoxome (the encapsulated form of daunorubicin).

Early in the 20th century, only cancers small and localized enough to be completely removed by surgery were curable. Later, radiation was used after surgery to control small tumor growths that were not surgically removed. Finally, chemotherapy was added to destroy small tumor growths that had spread beyond the reach of the surgeon and radiotherapist. The use of chemotherapy after surgery to destroy the few remaining cancer cells in the body is called adjuvant therapy. Adjuvant therapy was tested first in breast cancer and found to be effective. It was later used in colon cancer, cancer of the testis, and others.

A major discovery was the advantage of using multiple chemotherapy drugs (known as combination chemotherapy) over single agents. Some types of very fast-growing leukemias and lymphomas (tumors involving the cells of the bone marrow and lymph nodes, respectively) responded very well to combination chemotherapy, and clinical trials led to gradual improvement of the drug combinations used. Many of these tumors can be cured today by appropriate combination chemotherapy.

The approach to patient treatment has become more scientific with the introduction of clinical trials on a wide basis throughout the world. These clinical trials compare new treatments to standard treatments and contribute to a better understanding of treatment benefits and risks. Clinical trials test theories about cancer learned in the basic science laboratory and also test ideas derived from the clinical observations on cancer patients. They are necessary for continued progress.

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Cancer treatments: Immunotherapy
Better understanding of the biology of cancer cells has led to the development of biologic agents that mimic some of the natural signals that the body uses to control growth. Clinical trials have shown that this cancer treatment, called biological response modifier (BRM) therapy, biologic therapy, biotherapy, or immunotherapy, is effective for several cancers.

Some of these biologic agents, which occur naturally in the body, can now be made in the lab. Examples are interferons, interleukins, and other cytokines. These agents are given to patients to imitate or influence the natural immune response either by directly altering the cancer cell growth or acting indirectly to help healthy cells control the cancer.

One of the most exciting applications of biologic therapy has come from identifying certain tumor targets, called antigens, and aiming an antibody at these targets. This method was first used to find tumors for diagnosis and more recently has been used to attack cancer cells. Using technology first developed during the 1970s, scientists can mass produce monoclonal antibodies that are specifically targeted to chemical components of cancer cells. Refinements to these methods, using recombinant DNA technology, have improved the effectiveness and decreased the side effects of these treatments. The first therapeutic monoclonal antibodies, rituximab (Rituxan) and trastuzumab (Herceptin) were approved during the late 1990s for treating lymphoma and breast cancer, respectively. Studies are now being done to see if and how well these drugs work in other cancers, too. At least 9 monoclonal antibodies now are being used for cancer treatment, and many more are being studied.

Scientists are also studying vaccines that boost the body’s immune response to cancer cells. For instance, a 2009 lymphoma study looked at personalized vaccines made from tissue from each patient's tumor. Encouraging results showed that patients who received the vaccine lived longer disease-free than those who did not.

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Cancer treatments: Targeted therapy
Until the late 1990s nearly all drugs used in cancer treatment (with the exception of hormone treatments) worked by killing cells that were in the process of replicating their DNA and dividing to form 2 new cells. These chemotherapy drugs also killed some normal cells but, fortunately, had a greater effect on cancer cells.

Targeted therapies work by influencing the processes that control growth, division, and spread of cancer cells, as well as the signals that cause cancer cells to die naturally (the way normal cells do when they are too old). Targeted therapies work in several ways.

Growth signal inhibitors: Growth factors are hormone-like substances that help tell cells when to grow and divide. Their role in fetal growth and repair of injured tissue was first recognized during the 1960s. Later it was realized that abnormal forms or abnormally high levels of the same factors contribute to the growth and spread of cancer cells. Researchers have also started to understand how cells recognize these factors, and how that recognition leads to signals inside the cells that cause the abnormal features of cancer cells. Changes in these signal pathways have also been recognized as causing the abnormal behavior of cancer cells.

During the 1980s, scientists found that many of the growth factors and other substances responsible for growth factor recognition and signaling are actually products of oncogenes. Among the earliest targeted therapies that block growth signals are trastuzumab (Herceptin), gefitinib (Iressa), imatinib (Gleevec), and cetuximab (Erbitux). Current research has shown great promise for these treatments in some of the more difficult to treat and deadly forms of cancer, such as non-small cell lung cancer, advanced kidney cancer, and glioblastoma.

Angiogenesis inhibitors: Angiogenesis is the creation of new blood vessels. The term comes from 2 Greek words: angio, meaning "blood vessel," and genesis, meaning "beginning." Normally, this is a healthy process. New blood vessels, for instance, help the body heal wounds and repair damaged tissues. But in a person with cancer, this same process creates new, very small blood vessels that give a tumor its own blood supply and allow it to grow. Anti-angiogenesis is a form of targeted therapy that uses drugs or other substances to stop tumors from making the new blood vessels they need to continue growing. This concept was first proposed by Judah Folkman in the early 1970s, but it wasn't until 2004 that the first angiogenesis inhibitor, bevicizumab (Avastin) was approved for clinical use. Currently used to treat advanced colorectal, breast, and lung cancers, bevicizumab is being studied as treatment for many other types of cancer, too.

Apoptosis-inducing drugs: Apoptosis is a natural process through which cells with DNA too damaged to repair -- such as cancer cells -- can be forced to die. Many anti-cancer treatments (including radiation and chemotherapy) cause cell changes that eventually lead to apoptosis. But targeted drugs in this group are different, because they are aimed specifically at the cell substances that control cell survival and death.

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Cancer survivorship
Only a few decades ago, the prognosis (outlook) for people facing cancer was not nearly as favorable as it is today. During the 1970s, about 1 of 2 people diagnosed with cancer survived at least 5 years. Now, more than 2 of 3 survive that long. Today there are more than 11 million cancer survivors in the United States alone.

Now that more people are surviving cancer, more attention than ever is focused on the quality of life and long-term outcomes of cancer survivors. Behavioral researchers are working to learn more about the problems survivors face. Some of these problems are medical, such as permanent side effects of treatment, the possibility of second cancers caused by treatment, and the need for long-term medical follow-up. Other problems are emotional or social challenges, like getting health insurance, discrimination by employers, relationship changes that may result from life-threatening illness, or learning to live with the possibility of cancer coming back.

Cancer was once a word that people were afraid to speak in public, and people rarely admitted to being a cancer survivor. Now, many celebrities and national leaders have very openly discussed their cancer experiences.

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Buckwirth
Posts: 1272
Joined: Jun 2010

The twenty-first century and beyond
The growth in our knowledge of cancer biology has led to remarkable progress in cancer prevention, early detection, and treatment in recent years. Scientists have learned more about cancer in the last 2 decades than has been learned in all the centuries preceding. This does not change the fact, however, that all scientific knowledge is based on the knowledge already acquired by the hard work and discovery of our predecessors -- and we know that there is still a lot more to learn.

Cancer research is currently advancing on so many fronts that it is difficult to choose the ones to highlight here.

More targeted therapies: As more is learned about the molecular biology of cancer, researchers will have more targets for their new drugs. Along with more monoclonal antibodies and small signaling pathway inhibitors, researchers are developing new classes of molecules such as antisense oligodeoxynucleotides and small interfering RNA (siRNA).

An example of this is a new class of targeted therapies called PARP inhibitors. (PARP is short for poly (ADP-ribose) polymerase enzymes.) Cancer cells use PARP to repair DNA damage, including the damage caused by cancer treatment. Recent studies in breast cancer have shown that blocking PARP can make cancer cells more sensitive to treatment and promote cell death.

Nanotechnology: New technology for producing materials that form extremely tiny particles is leading to very promising imaging tests that can more accurately show the location of tumors, as well as new ways to deliver drugs more specifically and effectively to cancer cells.

Robotic surgery: This term refers to manipulation of surgical instruments remotely by robot arms and other devices controlled by a surgeon. Robotic systems have been used for several types of cancer surgery; radical prostatectomy is among the most common uses in surgical oncology. As mechanical and computer technology improve, some researchers expect future systems will be able to remove tumors more completely and with less surgical trauma.

RNA expression profiling and proteomics: RNA expression profiling lets scientists determine relative amounts of hundreds or even thousands of RNA molecules at one time. Knowing what proteins or RNA molecules are present in cells can tell scientists a lot about how the cell is behaving. In cancer, it can help distinguish more aggressive cancers from less aggressive ones, and can often help predict which drugs the tumor is likely to respond to. Proteomic methods are also being tested for cancer screening. For most types of cancer, measuring the amount of one protein in the blood is not very good at finding early cancers. But researchers are hopeful that comparing the relative amounts of many proteins may be more useful, and that knowing certain proteins are abnormally abundant and others are less abundant can provide accurate, useful information. This is an exciting area of research and early results in lung and colorectal cancer studies have been promising.

PGLGreg's picture
PGLGreg
Posts: 741
Joined: Jul 2006

I just wonder whether "photon" in the following sentence might be a typographical error: "Intensity-modulated radiation therapy, is like CRT but along with aiming photon beams from several directions, the intensity (strength) of the beams can be adjusted."

--Greg

Buckwirth's picture
Buckwirth
Posts: 1272
Joined: Jun 2010

I copy and pasted directly from the cancer.org page

John23
Posts: 1832
Joined: Jan 2007

Re:
"It's a pattern I've noticed in your replies. Someone brings up a
question or a point and you answer in a way that changes the subject. "

Your comments are well taken. I really do have other things to do,
than use my ideology and personal "feelings" in an attempt to convince
cancer sufferers that there is something else that may work as well,
or better than chemotherapy.

But alas, you're right. There is nothing else.

So long folks, sorry for wasting everyone's time with my idle banter.

Best of health to all.

John

lisa42's picture
lisa42
Posts: 3663
Joined: Jul 2008

John,

"So long folks, sorry for wasting everyone's time with my idle banter"... I do think you're being facecious (sp?) here and that you're tired of the arguments back and forth. Don't let someone else drive you away- everyone has something to offer and no one else should make them feel as if they don't! Some who think they know everything (but then say they don't and are researching, but still make others feel everything they say is invalid) are not right in exerting their forceful thoughts so much.

Ok, maybe I've exerted some forceful thoughts but in a different way, but I don't believe I've ever been disrespectful to others. Don't go...

Lisa

John23
Posts: 1832
Joined: Jan 2007

No, I'm not going anyplace, but I am giving up trying to provide
insight to those that wish to remain blind.

"Give us the grace to accept with serenity the things that cannot be changed,
Courage to change the things which should be changed,
And the wisdom to distinguish the one from the other."

(E. Sifton - The Serentiy Prayer)

Best of health!

John

PGLGreg's picture
PGLGreg
Posts: 741
Joined: Jul 2006

Well, that's okay, John. We're gradually getting some sense of the trend of your thought. It's interesting (though wrong). But I'm sure I speak for many of us when I say how happy I am that you are well enough to mount a spirited pursuit of your critique of modern oncology.

--Greg

Buckwirth's picture
Buckwirth
Posts: 1272
Joined: Jun 2010

Really?

Just because I asked you to stop using the straw man argument?

Kind of immature isn't it? Or is it an attempt to make the many friends you have on this board (and I count myself among them, I am concerned about you) to come to your defense and try to make me go away?

"Your comments are well taken. I really do have other things to do,
than use my ideology and personal "feelings" in an attempt to convince
cancer sufferers that there is something else that may work as well,
or better than chemotherapy."

In case you have missed it, I'm no great fan of chemotherapy, and believe that it is overused.

My challenge to you has been to convince me. And yes, when I posted that the Chinese claim a 13% survival rate, I was challenging you in particular.

Let me help with that one. The Chinese have not done as much as us with early detection, thus catching cancers in later stages, thus having a much lower survival rate.

But I wanted that to come from you, because I ask that you have an honest discussion. In the post above all I ask again is that you join me in an honest discussion.

Why?

Because I believe that there are things out there that can help people, maybe not cure their cancer, but help with the nausea, help with the fatigue, help with the myriad of other side effects we suffer in our treatments. I also believe there are more things that either do nothing or do harm. Wheat and Chaff. Sorting through that in this age of information overload is akin to cleaning out the Augean stables, truly a Herculean task.

Sadly, I think there are only a couple of people on this board capable of having such a discussion, and I thought you might be one of them.

usakat's picture
usakat
Posts: 626
Joined: Jul 2006

You provided some good info. Cancer can be a bit of an enigma for many of us, an unseen foreign invader that twists our minds as much as our bodies. Understanding the who, what, where, why of cancer can help some people cope with what is happening inside their own body - and in many cases make better choices for treatment and in life in general.

One of my favorite books of last year is, The Emperor of All Maladies, A Biography of Cancer, by Dr. Siddhartha Mukherjee. It is not only fascinating, but the book really opened my eyes and my mind about the subject of cancers. The book is a great read and written in a way that makes it readable and engaging for those of us without the title of MD or PhD.

I highly recommend this book.

Buckwirth's picture
Buckwirth
Posts: 1272
Joined: Jun 2010

to my iPad!

Thanks for the recommendation!

Blake

usakat's picture
usakat
Posts: 626
Joined: Jul 2006

I suspect you'll like the book...let me know what you think about it...

lisa42's picture
lisa42
Posts: 3663
Joined: Jul 2008

Hi Blake,

I truly do find this history of cancer information that you've posted interesting- really!Thank you for the info.
But, I must say that I wish you would watch how you respond to others. Granted, you have said in some that you don't mean disrespect even if you disagree, but it becomes tiresome to see you jump on everyone with something to say that you don't agree with. I'm not only referring to myself, but to several others. You seem to go hot and cold- jump on what they say and post an article to disprove it (and I do think all articles and studies need to be looked at carefully as there seems to always be articles and studies supporting opposite opinions- depends upon how the study was conducted and for what purpose). Then you go and apologize to someone telling them you mean no disrespect. Just doesn't make sense to me. I respect that you are trying to research and learn about cancer- that's what you say, but then you still jump on people for stating what they've done that seems to help them.
The inconsistency is confusing and frustrating to me.
Sorry- I just felt the need to say that, as there have been many posts and replies by you lately that seem to be "hot and cold", for lack of a better term.
Let's all just keep supporting each other & if someone doesn't agree, well putting up articles is fine, but let's not make the person feel as if what they are doing can't possibly be beneficial (even when the person just finished stating how it WAS beneficial for them).

Thanks-
Lisa

Buckwirth's picture
Buckwirth
Posts: 1272
Joined: Jun 2010

And jumped into this post, which was never intended for debate.

That said, I would enjoy a real debate with him on this site. There are many who share his views but few who are as capable as he in defending them.

Can you find an error is my response to him? An insult? Do you think he meant "Bucky" as a friendly pejorative?

Was this the place to begin a screed about the great cancer conspiracy?

"...but let's not make the person feel as if what they are doing can't possibly be beneficial (even when the person just finished stating how it WAS beneficial for them)."

Lisa,

When someone posts that the $2k they just spent on a water ionizer was the best investment they have ever made, do you not think that it encourages others to make the same choice? If someone knows that it is bunk, should they not point that out? It is, after all, a public forum where we are trying to help one another, an preventing someone else from throwing away $2k is helping.

John and others encourage people to do the research, well, I am doing it. Apparently no one actually means that when they say it.

usakat's picture
usakat
Posts: 626
Joined: Jul 2006

...and sometimes not. Thankfully our collective understanding of cancer is changing and improving everyday whether any of us recognize or believe it or not. Either way, survival rates are improving, early detection is improving, and people affected by cancer are living longer and more productive lives.

Just like hearts some minds cannot be changed and that is when we must "let it be"....

Oddly comforting though, having not posted for quite sometime, that things are still movin' and shakin' in the ol' neighborhood.

La di da di di...La di da di da....

Buckwirth's picture
Buckwirth
Posts: 1272
Joined: Jun 2010

Love it!

Thanks,

Blake

Annabelle41415's picture
Annabelle41415
Posts: 4264
Joined: Feb 2009

Thanks for sharing that with us. Very interesting. Just talking to another fellow colorectal person and he said that his surgeon and oncologist said that what he ate and drank had nothing to do with his cancer. He never eats sugar - never. Eats red meat about 3 times a year. His oncologist said that they aren't sure what caused it. I'm falling in the same category too. Just never made sense to me. Thanks for this.

Kim

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