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The History of Cancer
What Is Cancer?

Cancer develops when cells in a part of the body begin to grow out of control. Although there are many kinds of cancer, they all start because of out-of-control growth of abnormal cells.

Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide more rapidly until the person becomes an adult. After that, cells in most parts of the body divide only to replace worn-out or dying cells and to repair injuries.

Because cancer cells continue to grow and divide, they are different from normal cells. Instead of dying, they outlive normal cells and continue to form new abnormal cells.

Cancer cells often travel to other parts of the body where they begin to grow and replace normal tissue. This process, called metastasis, occurs as the cancer cells get into the bloodstream or lymph vessels of our body. When cells from a cancer like breast cancer spread to another organ like the liver, the cancer is still called breast cancer, not liver cancer.

Cancer cells develop because of damage to DNA. This substance is in every cell and directs all its activities. Most of the time when DNA becomes damaged the body is able to repair it. In cancer cells, the damaged DNA is not repaired. People can inherit damaged DNA, which accounts for inherited cancers. Many times though, a person's DNA becomes damaged by exposure to something in the environment, like smoking.

Cancer usually forms as a solid tumor. Some cancers, like leukemia, do not form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow.

Not all tumors are cancerous. Benign (noncancerous) tumors do not spread to other parts of the body (metastasize) and, with very rare exceptions, are not life threatening.

Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer.

Cancer is the second leading cause of death in the United States. Half of all men and one-third of all women in the US will develop cancer during their lifetimes. Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking and eating a better diet. The sooner a cancer is found and treatment begins, the better are the chances for living for many years.


Oldest Descriptions of Cancer

Cancer has afflicted humans throughout recorded history. It is no surprise that from the dawn of history doctors have written about cancer. Some of the earliest evidence of cancer is found among fossilized bone tumors, human mummies in ancient Egypt, and ancient manuscripts. Bone remains of mummies have revealed growths suggestive of the bone cancer, osteosarcoma. In other cases, bony skull destruction as seen in cancer of the head and neck has been found.

Our oldest description of cancer (although the term cancer was not used) was discovered in Egypt and dates back to approximately 1600 B.C. The Edwin Smith Papyrus, or writing, describes 8 cases of tumors or ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."


Origin of the Word Cancer

The origin of the word cancer is credited to the Greek physician Hippocrates (460-370 B.C.), considered the "Father of Medicine." Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab. Carcinoma is the most common type of cancer.


Renaissance Period

During the Renaissance, beginning in the 15th century, scientists in Italy developed a greater understanding of the human body. Scientists such as Galileo and Newton began to use the scientific method, which later began to be used to study disease. Autopsies, performed by Harvey (1628), allowed an understanding of the circulation of blood through the heart and body that had remained a mystery.

In 1761, Giovanni Morgagni of Padua was the first to do something considered routine today. He performed 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.


Nineteenth Century

The 19th century saw the birth of scientific oncology with the discovery and use of the modern microscope. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer. As Morgagni had correlated the autopsy findings observed 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 to a patient 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. In addition, the pathologist could tell the surgeon whether the operation had completely removed the tumor.


Cancer Causes

From the earliest times, physicians have wondered about the cause of cancer. The Egyptians blamed cancers on the Gods.

Humoral Theory: Hippocrates believed that the body contained 4 humors (body fluids) - blood, phlegm, yellow bile, and black bile. A balance of these fluids resulted in a state of health. Any excesses or deficiencies caused disease. An excess of black bile collecting 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 Hofman theorized that cancer was composed of fermenting and degenerating lymph varying in density, acidity, and alkalinity. The lymph theory gained rapid support. 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 was of the opinion 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: 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: Despite advances in the understanding of cancer, from the late 1800s until the 1920s, cancer was thought by some to be caused by trauma. This belief was maintained despite the failure to cause cancer in experimental animals by injury.

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.

A Nobel Prize was wrongly awarded in 1926 for scientific research documenting stomach cancer being caused by a certain worm. With the inability to confirm this research, scientists lost interest in the parasite theory.


Modern Day Carcinogens

More recently, other causes of cancer were discovered and documented. In 1911 Peyton Rous, at the Rockefeller Institute in New York, described a 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 .In 1915 cancer was induced in laboratory animals for the first time by a chemical, coal tar, applied to rabbit skin at Tokyo University. One hundred and fifty years had passed since the most destructive source of chemical carcinogens known to man, tobacco, was first identified in London by the astute clinician John Hill. It was to be many years until tobacco was "rediscovered" as a carcinogen.

Today we recognize and avoid many specific substances that cause cancer: coal tars and their derivatives such as 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 lead to cancer. To ensure the public's safety, the government has set occupational standards for many substances, such as benzene, asbestos, hydrocarbons in the air, arsenic in drinking water, radiation, and so on.

Several viruses are now linked to cancer:
  • Long-standing liver infection with the hepatitis virus can lead to cancer of the liver.
  • A variety of the herpes virus, the Epstein-Barr virus, causes infectious mononucleosis and has been implicated in non-Hodgkin's lymphomas and nasopharyngeal cancer.
  • The human immunodeficiency virus (HIV) is associated with an increased risk of developing several cancers, especially Kaposi's Sarcoma and non-Hodgkin's lymphoma.
  • Human papilloma viruses (HPVs) have been linked to cancers of the cervix, vulva, and penis.

Many of these associations were recognized long before scientists understood the mechanism by which the cancer was produced


Cancer Epidemiology

During the 18th century, 3 important observations were made that launched the field of cancer epidemiology.

    Bernardino Ramazzini, an Italian doctor, reported in 1713 the virtual absence of cervical cancer and relatively high incidence of breast cancer in nuns and wondered whether this was in some way related to their celibate lifestyle. This observation was an important step toward identifying and understanding the importance of hormonal factors such as pregnancy and infections related to sexual contact in modifying cancer risk.

    Percival Pott of Saint Bartholomew's Hospital in London described in 1775 an occupational cancer in chimney sweeps, cancer of the scrotum, caused by soot collecting under their scrotum. This research led to many additional studies that identified a number of occupational carcinogenic exposures and led to public health measures to reduce cancer risk.

    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.


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 patients have of the disease. Some people, even today, consider all cancer incurable and delay consulting a doctor until it is too late.

Treatments for cancer went 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 specifically in 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, there emerged the great surgeons 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 at Johns Hopkins. Their work led to "cancer operations" designed to remove all of the tumor together 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 be curative -- 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 it was replaced by the work of modern surgeons through clinical trials. Today, the radical mastectomy is almost never performed and the "modified radical mastectomy" is performed less frequently than before. In many cases, local removal of the primary tumor (lumpectomy) coupled with radiation therapy and chemotherapy is equally effective and much less disabling than the radical procedures.

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 of 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.

Less invasive surgical techniques are being studied and/or used. Cryosurgery (also called cryotherapy or cryoablation) is a surgical technique being studied to treat localized prostate cancer by freezing the cells with a metal probe. It is less invasive than radical prostatectomy, so there is less blood loss, a shorter hospital stay, a shorter recovery period, and less pain than radical surgery.


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 the improvement of 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, for the treatment and prevention of 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 following removal of the testes. Later, drugs that blocked male hormone were found to be effective treatment for prostate cancer, and these drugs are now being studied to determine if they have a role in prevention of prostate cancer.

New drugs to block the effects of male hormones and prevent prostate cancer growth are being developed. Studies are also underway to find the most effective combination of current hormonal treatments and to determine the value of using hormone therapy before or after radiation therapy. Studies of intermittent hormone therapy are also in progress.


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 the treatment of 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 therapeutic response. The methods and the machines for delivery of radiation therapy have steadily improved. Today, radiation is delivered with great precision in order to destroy malignant tumors while minimizing damage to adjacent normal tissue.

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 technology are making it possible to aim radiation more precisely than in the past. This method, called conformal radiation therapy, helps to treat only the area involved by the cancer. Radiation is focused to avoid the normal tissues as much as possible. This is expected to increase the effectiveness and reduce the side effects of radiation therapy. Studies are in progress to find out which radiation techniques are best suited for specific categories of patients.

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 side effects of nearby normal tissues.

Stereotactic surgery 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 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 ongoing 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 directly to the cancer or the adjacent tissues after the cancer has been removed. It is more commonly used in abdominal or pelvic cancers and in cancers that have a tendency to return. 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, thus allowing a higher dose of radiation to the cancer.

Research into this type of treatment is ongoing. The disadvantage of IORT is that, unless a dedicated machine is available in the operating room, the patient must be transported to the radiation therapy department during the procedure to receive the treatment and then returned to the operating room to complete the surgery.

Hyperthermia refers to the use of heat. Heat has been found to kill cancer cells, but when used alone, it does not destroy enough cells to cure the cancer. Heat, delivered by microwaves or ultrasound, has been studied in combination with radiation and may, in some instances, enhance the effect of the radiation.

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 ongoing to find substances that may protect normal cells from radiation.

Boron neutron capture therapy is an experimental type of radiation therapy that is sometimes used in brain tumors. A compound containing the element, boron, is injected into the patient's blood and concentrates in the brain tumor. The brain is then irradiated with neutrons from a nuclear reactor. When a neutron hits a boron atom, a type of radiation is released that has high energy but does not extend far into the surrounding normal brain tissue. The value of this approach remains to be determined.


Cancer Treatments: Chemotherapy

The century of the surgeon had begun with the discovery of anesthesia in 1846. Fifty years later, in 1896, Roentgen presented his famous paper on the X-ray. During World War II, naval personnel who were exposed to mustard gas as a result of a military action were found to have severe bone marrow depression. During that same period, the U.S Army was studying a number of agents related to mustard gas in order to develop more effective agents and to develop protective measures. In the course of that work, a compound called nitrogen mustard was studied and found to have substantial activity 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 proliferating 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 acute leukemia in children. Aminopterin blocked a critical chemical reaction needed for DNA replication. That drug was the predecessor of methotrexate, a commonly used cancer treatment drug today. Since then, other researchers discovered drugs that blocked different functions involved in cell growth and replication. The era of chemotherapy had begun. The first cure of metastatic cancer was obtained in 1956 when methotrexate was used to treat a rare tumor called choriocarcinoma.

Over the years, the development and use of chemotherapy drugs have resulted in the successful treatment of many people with cancer. Other cancers that can now be cured regularly with chemotherapy, even when widespread, include acute childhood leukemia, testicular cancer, and Hodgkin's Disease. Many other cancers can be controlled for long periods of time, even if not cured Now several approaches are being studied to improve the activity and reduce the undesirable 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 and chemoprotective agents (such as dexrazoxane and amifostine)
  • Hematopoietic stem cell transplantation
  • Agents that overcome multidrug resistance

Liposomal therapy is a new technique that uses chemotherapy drugs that have been packaged inside liposomes (synthetic fat globules). This liposome, or fatty coating, helps them penetrate the cancer cells more selectively and decreases possible side effects (such as hair loss, nausea, and vomiting). Examples of liposomal medications are Doxil (the encapsulated form of doxorubicin) and Daunoxome (the encapsulated form of daunorubicin).

Monoclonal antibodies, a special type of antibody produced in laboratories, can be designed to guide chemotherapy medications directly to the tumor. Monoclonal antibodies (or proteins) bind to tumor-associated cell surface antigens and destroy tumor cells through a variety of methods.

Early in the 20th century, the only curable cancers were small and localized enough to be completely removed by surgery. 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 multiple chemotherapeutic agents (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 extremely 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 essential to continued progress.


Cancer Treatments: Biologic Therapy

Scientists' 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 regulate growth. This cancer treatment, called biological response modifier (BRM) therapy, biologic therapy, biotherapy, or immunotherapy, has proven effective for several cancers through the clinical trial process.

Some of these biologic agents, occurring naturally in the body, can now be produced in the laboratory. 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 localize tumors in the body for diagnosis and more recently has been used to attack cancer cells.

Scientists are also studying vaccines that would boost the body's immune response to cancer cells and thereby prevent cancer from developing.


Twentieth-Century Understanding of Cancer

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 presented by cancer. James Watson and Francis Crick, who received the Nobel Prize 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 our understanding of DNA and genes increased, we learned that it was the damage to DNA by chemicals and radiation or 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.

Further, scientists discovered that sometimes defective genes are inherited and that sometimes these inherited genes are defective at the same points that chemicals exerted their effect. In other words, most carcinogens caused genetic damage (mutations), mutations led to abnormal groups of cells (called clones), 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 recent discovery of this critical difference answers many questions that have troubled scientists for many years.

Slowly, medical scientists are identifying the genes that are damaged by chemicals or radiation and the genes that, when inherited, can lead to cancer. The recent discovery of two genes that cause some breast cancers, BRCA1 and BRCA2, represents considerable promise because many people who have a higher probability of developing breast cancer can now be identified

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


The Impact of Modern Biology on Cancer Treatment

The knowledge of molecular biology and genetics that is coming from basic science laboratories throughout the world is already having an influence on cancer treatment as it is on cancer detection and diagnosis.

Angiogenesis is a normal process, the growth of new blood vessels, necessary for growth and for wound healing. It has recently been determined that in order for a tumor to grow, it must develop its own blood supply. Drugs have now been developed that, in laboratory animals, can prevent new blood vessels from developing. Some of these drugs are already in trial in human beings with cancer and are showing considerable promise.

Signal transduction is the complicated process by which growth signals are transmitted to the nucleus of the cell. Many efforts have been made to interfere with that signaling. One agent has been highly successful in a chronic form of leukemia (for which it is now being used regularly) and is showing promise in other cancers.

Genetic Therapy As we learn more about the molecular genetics of cancer, we are able to take advantage of specific genetic characteristics. For example, some patients with breast cancer have too many copies of a gene called Her2/neu. Scientists have been able to develop an antibody called trastuzumab (Herceptin) that is active against cancer in those patients.

The fact that specific defects can be related to individual kinds of cancer and that, in at least a few cases, can be turned into powerful, very specific tools provides promise that additional tools will be coming from our laboratories


Summary

The growth in our knowledge of cancer biology and cancer treatment and prevention has been staggering in recent years. Scientists have learned more about cancer in the last decade of the 20th century 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.


Additional Resources

Encyclopedia Britannica. See entries on Medicine, History of Cancer.

Lyons AS, Petrucelli RJ. Medicine: An Illustrated History. New York: Harry N. Abrams Publishers; 1978.

Shimkin MB. Contrary to Nature: Cancer. For sale by the Superintendent of Documents, U.S. Printing Office, Washington D.C. 20401. DHEW Publication No (NIH) 76-720; 1976.


References

Contran R, Kumar V, Robbins S. Robbins Pathologic Basis of Disease, 4th ed. Philadelphia, Pa: WB Saunders; 1989.

Diamandopoulus GT. Cancer: An historical perspective. Anticancer Res 1996;16:1595-1602.

Gallucci BB. Selected concepts of cancer as a disease: From the Greeks to 1900. Oncol Nurs Forum 1985;12:67-71.

Harvey AM. Early contributions to the surgery of cancer: William S. Halsted, Hugh H. Young and John G. Clark. Johns Hopkins Med J 1974;135:399-417.

Kardinal C, Yarbro J. A conceptual history of cancer. Semin Oncol 1979;6:396-408.

Meisels A, Morin C. Cytopathology of the Uterus. 2nd ed. ASCP Theory and Practice of Cytopathology 1. Chicago: ASCP Press; 1997.

Revised: 3/25/02
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