Who introduced the concept of chemotherapy?
[Cancer Res 2008;68 (21):8643–53] In the early 1900s, the famous German chemist Paul Ehrlich set about developing drugs to treat infectious diseases. He was the one who coined the term “chemotherapy” and defined it as the use of chemicals to treat disease.
Do oncologists who get cancer choose chemo?
Vast Majority of Oncologists Would NOT Use Chemotherapy If They Got Cancer “Over 75% of the oncologists polled said that if they had cancer they would never use the same chemotherapy they prescribe for their patients on themselves because of the ineffectiveness of chemotherapy and its unacceptable degree of toxicity.”
Who discovered Electroconvulsive therapy?
The history of ECT begins in the 1500s with the idea of treating mental illness with convulsions. Initially, convulsions were induced by orally taking camphor. The history of modern electroconvulsive therapy (ECT) dates back to 1938 when Italian psychiatrist Lucio Bini and neurologist Ugo Cerletti used electricity to induce a series of seizures ...
Who discovered esophagus cancer?
- First, we found that the main stomach enzyme, pepsin, was the bad actor. While it is still called “acid reflux,” it’s pepsin that causes inflammation, tissue damage, and perhaps cancer. ...
- Second, we found pepsin in every biopsy of laryngeal cancer that we studied.
- And finally, we found pepsin in biopsies of Barrett’s esophagus.
Who discovered cancer chemotherapy?
Research to practice: How the first chemotherapeutic agents were identified. The effects of mustard gas on blood cells and bone marrow were first reported by Dr Eward Krumbhaar in 1919 after treating exposed patients in France [6].
Who named the concept of chemotherapy?
DeVita Chemotherapy was first coined as a word by Paul Ehrlich, a chemist who was well known in the early 1900s. He defined it as using chemicals to treat syphilis.
When was chemo first introduced?
The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs.
Who was the first to use chemotherapy?
Babe Ruth was one of the first cancer patients to receive a combination of chemotherapy and radiation, a practice that doctors still use today.
Who is known as father of modern chemotherapy?
Sidney Farber, world-renowned paediatric pathologist, made major contributions to his field but is acknowledged as the father of the modern era of chemotherapy. He recognised that folic acid stimulated leukaemic cell growth and enhanced disease progression.
Is the father of chemotherapy?
Paul Ehrlich: Nobel laureate and father of modern chemotherapy.
Why is it called Salvarsan 606?
Arsphenamine was originally called "606" because it was the sixth in the sixth group of compounds synthesized for testing; it was marketed by Hoechst AG under the trade name "Salvarsan" in 1910.
Who invented radiotherapy?
Radiotherapy can be traced back about 125 years to the discovery of X-rays (1895) by a Germany physicist named W. C. Roentgen.
Why is it called chemotherapy?
The term chemotherapy has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy.
How did Paul Ehrlich Discover chemotherapy?
During his work with dyes, Ehrlich had tested the effects of methylene blue on malaria plasmodia, and so he first searched for drugs against parasites. Together with his postdoc, Shiga, he chose African trypanosomes as a target and trypan red as the drug, and soon established proof of principle in 1904.
Who contributed in the discovery of chemotherapeutic agents?
The researches of Louis Pasteur in France and Robert Koch in Germany laid the foundations of bacteriology. It was Paul Ehrlich, however, who made the greatest contribution to the science (chemotherapy) he named.
Who is Robert Sandler?
Robert Sandler is professor of medicine and epidemiology. He is a practicing gastroenterologist with research interests in the epidemiology of chronic digestive diseases.
When was chemo first used?
Chemotherapy was first developed at the beginning of the 20th century, although it was not originally intended as a cancer treatment. During World War II, it was discovered that people exposed to nitrogen mustard developed significantly reduced white blood cell counts.
When did cytotoxic agents start being used for cancer?
The scientists found that the patients tumour masses were significantly reduced for a few weeks after treatment and although the patient had to return to receive more chemotherapy, this marked the beginning of the use of cytotoxic agents for the treatment of cancer. The initial study was done in 1943 and the results were published in 1946.
When did vinca alkaloids become anticancer?
This led to the introduction of vinca alkaloids as anticancer agents in the 1960s. Examples include vinblastine used to treat Hodgkin's disease and vincristine used to treat pediatric leukemia. Over the next two decades, combination chemotherapy regimens started to gain popularity.
Who discovered mustard in the 1940s?
In the 1940s, two prominent Yale pharmacologists, Alfred Gilman and Louis Goodman examined the therapeutic effects of mustard agents in treating lymphoma. First, they established lymphomas in mice and showed that the tumors could be treated with mustard agents.
Is mustard good for lymphoma?
The use of nitrogen mustard for lymphomas gained popularity in the United States after the publication of the article in 1946. Nitrogen mustard and other derivatives of mustard gas are called alkylating agent due to their ability to alkylate molecules including protein, DNA and RNA.
Abstract
The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents.
Introduction
In the early 1900s, the famous German chemist Paul Ehrlich set about developing drugs to treat infectious diseases. He was the one who coined the term “chemotherapy” and defined it as the use of chemicals to treat disease.
The Early Period of Cancer Drug Development
A selected history and timeline of events related to the development of cancer chemotherapy is shown in Fig. 1. The first four decades of the 20th century were primarily devoted to model development.
World War II and the Immediate Post-War Period
Although gases were not used on the battlefield in World War II (WWII), a great deal of research was done on vesicant war gases ( 5, 8 ).
The 1950s
The 1950s were a period of undue pessimism due to the disappointment over the failed promise of nitrogen mustard to produce durable remissions. This negative view was somewhat offset by the discovery of corticosteroids, which were to be used in cancer patients but were also quickly found to produce only brief responses when used alone ( 31, 32 ).
The 1970s: The Age of Adjuvant Chemotherapy
The concept of cure had a remarkably permissive effect on the use of chemotherapy in earlier stages of cancers. For example, about 90% of patients with breast cancer present with locoregional disease. Yet, the majority will develop recurrences if only the best locoregional treatment is used.
Passage of the Cancer Act of 1971 and Beyond
One unanticipated benefit of the report of the curability of choriocarcinoma, lymphomas, and acute leukemias with combination chemotherapy was the passage of the National Cancer Act in 1971.
When did chemotherapy start?
The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.
Who is the father of modern chemo?
Sidney Farber 's work was instrumental in showing that effective pharmacological treatment of cancer was possible, and to this day, he is regarded as the father of modern chemotherapy. Shortly after World War II, a second approach to drug therapy of cancer began. Sidney Farber, a pathologist at Harvard Medical School, ...
What was the first chemical warfare agent?
The beginnings of the modern era of cancer chemotherapy can be traced directly to the German introduction of chemical warfare during World War I. Among the chemical agents used, mustard gas was particularly devastating. Although banned by the Geneva Protocol in 1925, the advent of World War II caused concerns over the possible re-introduction of chemical warfare. Such concerns led to the discovery of nitrogen mustard, a chemical warfare agent, as an effective treatment for cancer. Two pharmacologists from the Yale School of Medicine, Louis S. Goodman and Alfred Gilman, were recruited by the US Department of Defense to investigate potential therapeutic applications of chemical warfare agents. Goodman and Gilman observed that mustard gas was too volatile an agent to be suitable for laboratory experiments. They exchanged a nitrogen molecule for sulfur and had a more stable compound in nitrogen mustard. A year into the start of their research, a German air raid in Bari, Italy led to the exposure of more than 1000 people to the SS John Harvey 's secret cargo composed of mustard gas bombs. Dr. Stewart Francis Alexander, a lieutenant colonel who was an expert in chemical warfare, was subsequently deployed to investigate the aftermath. Autopsies of the victims suggested that profound lymphoid and myeloid suppression had occurred after exposure. In his report, Dr. Alexander theorized that since mustard gas all but ceased the division of certain types of somatic cells whose nature was to divide fast, it could also potentially be put to use in helping to suppress the division of certain types of cancerous cells.
What is the name of the drug that is used to treat spindle poison?
Clockwise from center: bleomycin, an antitumor antibiotic; vincristine, a spindle poison; dacarbazine, an alkylating agent; cyclophosphamide, a nitrogen mustard; doxorubicin, an anthracycline; and etoposide, a topoisomerase inhibitor. The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards ...
When did methotrexate cure choriocarcinoma?
Several years later at the National Cancer Institute, Roy Hertz and Min Chiu Li then demonstrated complete remission in women with choriocarcinoma and chorioadenoma in 1956, discovering that methotrexate alone could cure choriocarcinoma (1958) , a germ-cell malignancy that originates in trophoblastic cells of the placenta.
When was the National Cancer Chemotherapy Service Center established?
In response, Congress created a National Cancer Chemotherapy Service Center (NCCSC) at the NCI in 1955 . This was the first federal programme to promote drug discovery for cancer – unlike now, most pharmaceutical companies were not yet interested in developing anticancer drugs.
When was the first clinical trial of pharmacological agents?
Publication of the first clinical trials was reported in 1946 in the New York Times.
What is the purpose of chemotherapy?
Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms . Induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. This type of chemotherapy is used for curative intent.
When did the ASHP start regulating chemo?
In the 1970s, antineoplastic (chemotherapy) drugs were identified as hazardous, and the American Society of Health-System Pharmacists (ASHP) has since then introduced the concept of hazardous drugs after publishing a recommendation in 1983 regarding handling hazardous drugs. The adaptation of federal regulations came when the U.S. Occupational Safety and Health Administration (OSHA) first released its guidelines in 1986 and then updated them in 1996, 1999, and, most recently, 2006.
Why do cancer cells have resistance to chemotherapy?
Resistance is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes of resistance in cancer, one of which is the presence of small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Cancer cells produce high amounts of these pumps, known as p-glycoprotein, in order to protect themselves from chemotherapeutics. Research on p-glycoprotein and other such chemotherapy efflux pumps is currently ongoing. Medications to inhibit the function of p-glycoprotein are undergoing investigation, but due to toxicities and interactions with anti-cancer drugs their development has been difficult. Another mechanism of resistance is gene amplification, a process in which multiple copies of a gene are produced by cancer cells. This overcomes the effect of drugs that reduce the expression of genes involved in replication. With more copies of the gene, the drug can not prevent all expression of the gene and therefore the cell can restore its proliferative ability. Cancer cells can also cause defects in the cellular pathways of apoptosis (programmed cell death). As most chemotherapy drugs kill cancer cells in this manner, defective apoptosis allows survival of these cells, making them resistant. Many chemotherapy drugs also cause DNA damage, which can be repaired by enzymes in the cell that carry out DNA repair. Upregulation of these genes can overcome the DNA damage and prevent the induction of apoptosis. Mutations in genes that produce drug target proteins, such as tubulin, can occur which prevent the drugs from binding to the protein, leading to resistance to these types of drugs. Drugs used in chemotherapy can induce cell stress, which can kill a cancer cell; however, under certain conditions, cells stress can induce changes in gene expression that enables resistance to several types of drugs. In lung cancer, the transcription factor NFκB is thought to play a role in resistance to chemotherapy, via inflammatory pathways.
What is maintenance chemo?
Maintenance chemotherapy is a repeated low-dose treatment to prolong remission. Salvage chemotherapy or palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, in general, a better toxicity profile is expected.
Why do we need to repeat chemo?
Because only a fraction of the cells in a tumor die with each treatment ( fractional kill ), repeated doses must be administered to continue to reduce the size of the tumor. Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity.
How long does it take for chemo to cause side effects?
Chemotherapy-related toxicities can occur acutely after administration, within hours or days, or chronically, from weeks to years .
When is adjuvant chemotherapy given?
Adjuvant chemotherapy is given after a local treatment (radiotherapy or surgery). It can be used when there is little evidence of cancer present, but there is risk of recurrence. It is also useful in killing any cancerous cells that have spread to other parts of the body.
What was the first chemo drug?
It worked and nitrogen mustard, rechristened mustine, became the first licensed chemotherapy agent. Other drugs appeared in rapid succession, some triggered by biological insight, others by pure guesswork. One of the most striking of the former was aminopterin.
Who coined the term "cancer"?
The Roman physician Celsus, active in the first century BC, coined the word cancer from the Latin word for crab.
What was the first surgical innovation?
The discovery of general anaesthesia in the middle of the 19th century set off a golden age of surgical innovation. The American surgeon William Halsted pioneered radical cancer operations, attempting to outpace tumour growth by more and more extreme removal of tissue, in the belief – only partly true – that recurrence meant that some of the tumour had been left behind. He proved that surgeons could remove cancers, but whether patients were thereby cured was less clear. Some were, most were not.
What was the first anti-cancer drug?
Anti-cancer drugs made their entrance in the 1940s. In a grim paradox, the first was nitrogen mustard , a poison gas used to slaughter soldiers in the trenches of the First World War. Soldiers who survived exposure to it suffered the destruction of their lymphocytes – white blood cells – and needed regular blood transfusions. This selective action against a particular type of cell suggested that nitrogen mustard might be used to treat lymphoma, a tumour of the lymph system. It worked and nitrogen mustard , rechristened mustine, became the first licensed chemotherapy agent.
Why did the first cancer hospital in France move from the city of Reims?
1779 The first cancer hospital in France is forced to move from the city of Reims because people feared the disease would spread throughout the city. 1838 German pathologist Johannes Müller demonstrates that cancer is made up of cells and not lymph, but he believes cancer cells did not come from normal cells.
Where did cancer originate?
3000 BC The earliest known description of cancer is in an ancient Egyptian textbook on trauma. Known as the Edwin Smith Papyrus, it describes eight cases of tumours or ulcers of the breast that were removed by cauterisation with a tool called the fire drill. The document says of the disease: “There is no treatment”.
When was radiation first used for cancer?
Radiation came first, pioneered in 1896 by a medical student, Emil Grubbe, barely a year after Wilhelm Röntgen discovered X-rays.
When was cancer first discovered?
The First Documented Case of Cancer. The world's oldest documented case of cancer hails from ancient Egypt in 1500 BC. 2 The details were recorded on papyrus, documenting eight cases of tumors occurring on the breast.
What was wrongfully awarded for the discovery of stomach cancer?
In 1926, a Nobel Prize was wrongfully awarded for the discovery of the cause of stomach cancer, a worm. The 20th century saw the greatest progression in cancer research. Research identifying carcinogens, chemotherapy , radiation therapy, and better means of diagnosis was discovered.
What did Hippocrates call cancer?
Hippocrates used the Greek words carcinos and carcinoma to describe tumors, thus calling cancer "karkinos.". 1 The Greek terms actually were words that were used to describe a crab, which Hippocrates thought a tumor resembled.
What is the theory that cancer spreads like a liquid?
6 Other theories surfaced, such as cancer being caused by trauma, parasites, and it was thought that cancer may spread "like a liquid.".
When was blood circulation discovered?
Blood circulation was discovered, opening the doors for more research on diseases. It wasn't until 1761 that autopsies were performed to research the cause of death in ill patients. Giovanni Morgagni of Padua was the first to do such autopsies. 5 .
When was the lymphatic system discovered?
The lymph theory developed in the 17th century , replacing Hippocrates' black bile theory on the cause of cancer. The discovery of the lymphatic system gave new insight into what may cause cancer. It was believed that abnormalities in the lymphatic system were the cause. 3
Who caused cancer in ancient Egypt?
This was the general thought of the cause of cancer for the next 1,400 years. 4 In ancient Egypt, it was believed that cancer was caused by the Gods.
Who coined the term "leukemia"?
Rudolph Virchow identifies white blood cells (leukocytes) in cancerous tissue, making the first connection between inflammation and cancer. Virchow also coins the term "leukemia" and is the first person to describe the excess number of white blood cells in the blood of patients with this disease.
What was the first test to detect cervical cancer?
1928: The Pap Smear. George Papanicolaou discovers that cervical cancer can be detected by examining cells from the vagina under a microscope. This breakthrough leads to the development of the Pap test, which allows abnormal cervical cells to be detected and removed before they become cancerous.
How many types of cancer are there in the human body?
Researchers from The Cancer Genome Atlas (TCGA) project, a joint effort by NCI and the National Human Genome Research Institute to analyze the DNA and other molecular changes in more than 30 types of human cancer, find that gastric (stomach) cancer is actually four different diseases, not just one, based on differing tumor characteristics. This finding from TCGA and other related projects may potentially lead to a new classification system for cancer, in which cancers are classified by their molecular abnormalities as well as their organ or tissue site of origin.
How many cancer types are there in the pancancer?
NIH-funded researchers with TCGA complete an in-depth genomic analysis of 33 cancer types. The PanCancer Atlas provides a detailed genomic analysis of molecular and clinical data from more than 10,000 tumors that gives cancer researchers an unprecedented understanding of how, where, and why tumors arise in humans.
When was tamoxifen approved?
1978: Tamoxifen. FDA approves tamoxifen, an antiestrogen drug originally developed as a birth control treatment, for the treatment of breast cancer. Tamoxifen represents the first of a class of drugs known as selective estrogen receptor modulators, or SERMs, to be approved for cancer therapy.
How many genomes are there in cancer?
A consortium of international researchers analyzes more than 2,600 whole genomes from 38 types of cancer and matching normal tissues to identify common patterns of molecular changes. The Pan-Cancer Analysis of Whole Genomes study, which used data collected by the International Cancer Genome Consortium and TCGA, uncovers the complex role that changes throughout the genome play in cancer development, growth, and spread. The study also extends genomic analyses of cancer beyond the protein-coding regions to the complete genetic composition of cells.
What is the treatment for breast cancer?
Sir Geoffrey Keynes describes the treatment of breast cancer with breast-sparing surgery followed by radiation therapy . After surgery to remove the tumor, long needles containing radium are inserted throughout the affected breast and near the adjacent axillary lymph nodes.
Overview
Combination chemotherapy
In 1965, a major breakthrough in cancer therapy occurred. James F. Holland, Emil Freireich, and Emil Frei hypothesized that cancer chemotherapy should follow the strategy of antibiotic therapy for tuberculosis with combinations of drugs, each with a different mechanism of action. Cancer cells could conceivably mutate to become resistant to a single agent, but by using different drugs concurrently it would be more difficult for the tumor to develop resistance to the combination. H…
Beginnings
The beginnings of the modern era of cancer chemotherapy can be traced directly to the German introduction of chemical warfare during World War I. Among the chemical agents used, mustard gas was particularly devastating. Although banned by the Geneva Protocol in 1925, the advent of World War II caused concerns over the possible re-introduction of chemical warfare. Such concerns led to the discovery of nitrogen mustard, a chemical warfare agent, as an effective trea…
Antifolates
Shortly after World War II, a second approach to drug therapy of cancer began. Sidney Farber, a pathologist at Harvard Medical School, studied the effects of folic acid on leukemia patients. Folic acid, a vitamin crucial for DNA metabolism (the significance of DNA was not known at that time), had been discovered by Lucy Wills, when she was working in India, in 1937. It seemed to stimulate the prolif…
6-MP
Joseph Burchenal, at Memorial Sloan-Kettering Cancer Center in New York, with Farber's help, started his own methotrexate study and found the same effects. He then decided to try to develop anti-metabolites in the same way as Farber, by making small changes in a metabolite needed by a cell to divide. With the help of George Hitchings and Gertrude Elion, two pharmaceutical chemists who were working at the Burroughs Wellcome Co. in Tuckahoe, many purine analogues were teste…
Vinca Alkaloids
The Eli Lilly natural products group found that alkaloids of the Madagascar periwinkle (Vinca rosea), originally discovered in a screen for anti-diabetic drugs, blocked proliferation of tumour cells. The antitumour effect of the vinca alkaloids (e.g. vincristine) was later shown to be due to their ability to inhibit microtubule polymerization alkaloys, and therefore cell division.
National Cancer Chemotherapy Service Center
The NCI, headed by Dr. John R. Heller Jr., lobbied the United States Congress for financial support for second-generation chemotherapy research. In response, Congress created a National Cancer Chemotherapy Service Center (NCCSC) at the NCI in 1955. This was the first federal programme to promote drug discovery for cancer – unlike now, most pharmaceutical companies were not yet interested in developing anticancer drugs. The NCCSC developed the methodologies and crucia…
Adjuvant therapy
As predicted by studies in animal models, drugs were most effective when used in patients with tumours of smaller volume. Another important strategy developed from this — if the tumour burden could be reduced first by surgery, then chemotherapy may be able to clear away any remaining malignant cells, even if it would not have been potent enough to destroy the tumor in its entirety. This approach was termed "adjuvant therapy".
Overview
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (pa…
History
The first use of small-molecule drugs to treat cancer was in the early 20th century, although the specific chemicals first used were not originally intended for that purpose. Mustard gas was used as a chemical warfare agent during World War I and was discovered to be a potent suppressor of hematopoiesis (blood production). A similar family of compounds known as nitrogen mustards were …
Treatment strategies
There are a number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.
• Induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. This type of chemotherapy is used for curative intent.
Adverse effects
Chemotherapeutic techniques have a range of side effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. Chemotherapy-related toxicities can occur acutely after administration, within hours or days, or chronically, from weeks to years.
Limitations
Chemotherapy does not always work, and even when it is useful, it may not completely destroy the cancer. People frequently fail to understand its limitations. In one study of people who had been newly diagnosed with incurable, stage 4 cancer, more than two-thirds of people with lung cancer and more than four-fifths of people with colorectal cancer still believed that chemotherapy was likely to cure their cancer.
Resistance
Resistance is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes of resistance in cancer, one of which is the presence of small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Cancer cells produce high amounts of these pumps, known as p-glycoprotein, in order to protect themselves from chemotherapeutics. Research on p-glycoprotein and other such chemotherapy …
Cytotoxics and targeted therapies
Targeted therapies are a relatively new class of cancer drugs that can overcome many of the issues seen with the use of cytotoxics. They are divided into two groups: small molecule and antibodies. The massive toxicity seen with the use of cytotoxics is due to the lack of cell specificity of the drugs. They will kill any rapidly dividing cell, tumor or normal. Targeted therapies are designed to affect cellular proteins or processes that are utilised by the cancer cells. This all…
Mechanism of action
Cancer is the uncontrolled growth of cells coupled with malignant behaviour: invasion and metastasis (among other features). It is caused by the interaction between genetic susceptibility and environmental factors. These factors lead to accumulations of genetic mutations in oncogenes (genes that control the growth rate of cells) and tumor suppressor genes (genes that help to prevent cancer), …