TIMELINE OF CANCER
Mr. Naveen Kadian
What is Cancer?
A term for diseases in which abnormal cells divide without control and
can invade nearby tissues. Cancer cells can also spread to other parts
of the body through the blood and lymph systems.
Oldest Description of Cancer
Our oldest description of cancer (although the word cancer was
not used) was discovered in Egypt and dates back to about 3000 BC. It
is called the Edwin Smith Papyrus and is a copy of part of an ancient
Egyptian textbook on trauma surgery.
It 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 word Cancer
The origin of the word cancer is credited to the Greek physician
Hippocrates (460-370BC), who 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.
The Roman physician, Celsus (28-50 BC), later translated the Greek
term into cancer, the Latin word for crab.
Galen (130-200 AD), another Roman physician, used the word oncos
(Greek for swelling) to describe tumors.
Although the crab analogy of Hippocrates and Celsus is still used to
describe malignant tumors, Galen’s term is now used as a part of the
name for cancer specialists — oncologists.
Evidence of cancer:
Signs of cancer are found on the bones of mummies from ancient Egypt
and Peru dating back as far as 3000 BC.
The Edwin Smith Papyrus, which is the oldest written description of
cancer known to exist, describes eight cases of breast tumors or ulcers in
Egypt that were treated with cauterization. However, the document also
states that there is no treatment for cancer. The original document, written
in 3000 BC, was acquired in 1862 by Edwin Smith at Luxor, Egypt.
Oldest specimens of cancer
(1900 BC to 1500 BC)
Oldest available specimen of a human cancer is found in the
remains of skull of a female who lived during the Bronze Age (19001600 BC) The tumor in the women's skull was suggestive of head and
neck cancer. The mummified skeletal remains of Peruvian Incas, dating
back 2400 years ago, contained abnormalities suggestive of
involvement with malignant melanoma. Cancer was also found in
fossilized bones recovered from ancient Egypt.
One of the earliest human cancers found in the remains of mummies
was a bone cancer suggestive of osteosarcoma.
Louis Leakey found the oldest possible hominid malignant tumor in
1932 from the remains of either a Homo erectus or an
Australopithecus. This tumor was suggestive of a Burkitt’s
lymphoma (although that nomenclature was certainly not in use
then). Diseases that we know to be rare cancers today have had a
Hippocrates: known today as the father of medicine,
proposed the Humoral Theory of Medicine, which
states that the body is composed of four fluids, or
humors: blood, phlegm, yellow bile, and black bile.
Any imbalance of these fluids was thought to cause
disease. He attributed cancer to an excess of black
He believed that it was best to leave cancer alone
because those who got treatment didn't survive as
Hippocrates is credited with being the first to
recognize the difference between benign and
Galen: a Roman physician, was also a
believer in the Humoral Theory of Medicine.
He believed cancer to be curable in early
stages, and that advanced tumors should be
operated upon either by cutting around the
affected area or by cauterization. Galen
thought that unhealthy diet and bad climate
were directly connected to cancer.
Paul of Aegina: One of the most
prominent Byzantine physicians, wrote a
seven volume Epitome of Medicine. In his
opinion, cancer of the breast and uterus
were the most common. In the sixth book
of the Epitome, exclusively to do with
surgery, he asserted that surgery on uterine
cancer was useless. For breast cancer, he
recommended removal as opposed to
Moses Maimonides: a prominent
physician, scientist, and philosopher,
wrote ten medical treatises. His fifth
treatise contains surgical aphorisms, some
of which pertain to his treatment of cancer.
His treatment of large tumors, as he wrote,
involves "excising the tumor and uproots
the entire tumor and its surroundings up to
the point of healthy tissue, except if the
tumor contains large vessels&/or the
tumor happens to be situated in close
proximity to any major organ, excision is
Bernardino Ramazzini: noticed the virtual
absence of cervical cancer among nuns, and the
high incidence of breast cancer within the same
population. He concluded that this difference
must be due to their different lifestyle, namely
their abstinence. This observation lead the way
to discovering the importance of hormonal
factors in cancer. His work is a very early
example of an epidemiological study. He is
also known as the 'father' of occupational health
for authoring his most well known work - De
Morbis Artificum Diatriba (Diseases of
In 1727, however, Le Clerc suggested cutting out swellings, polyps,
and tumefactions before they became cancerous.
Giovanni Morgagni began performing
autopsies to relate illness to pathological
findings,. This helped to set a foundation
for the study of cancer.
John Hill first recognized an environmental
cause from the dangers of tobacco use in
1761 and published a book “Cautions
Against the Immoderate Use of Snuff”.
Percival Pott showed that chimney sweeps
had an occupation-related cancer risk. Soot
that collected under their scrotum was
associated with scrotal cancer. This discovery
lead to additional studies which identified
other occupational cancer risks. The
identification of these risks allowed public
health measures to be taken.
First cancer hospital founded in Reims, France. The hospital was
moved away from the city due to a widespread fear at the time that
cancer was contagious.
Joseph Claude Anthelm Recamier was the
first to recognize cancer metastasis. He listed
changes in eating habits as a cause of local,
acquired or spontaneous cancers.
Muller , a German
pathologist, published “On the Nature
and Structural Characteristics of
Cancer, and of Those Morbid Growths
Which May Be Confounded with It”,
which began to establish pathological
histology as an independent branch of
science. He demonstrated that cancer is
made up of cells, although he thought
that cancer cells arose from abnormal
cells. He believed that cancer cells
undifferentiated tissue from which it
was believed that cells arose from)
between normal tissues.
Advent of general anesthesia opens
the door for modern cancer surgery
In October 1846, a Boston
dentist named William T.G. Morton
demonstration of ether as a general
anesthetic, allowing surgeons to
remove a tumor from a patient’s jaw
without pain. This advance gains
immediate and widespread attention,
excruciating pain experienced by
surgical patients until that time, and
making the modern era of surgery
R.Virchow, a student of Muller'. He
wrote several papers and a three
volume work, Die krankhaften
Geschwlste, on malignant tumors.
He theorized that tumors were the
result of chronic irritation and that
cancer spread in a manner similar to
Billroth , a German
surgeon, performed the first pyloric
resection (surgical removal of all or
part of the stomach) for carcinoma.
He also was the first (in 1872) to
perform an esophageal resection for
Radical mastectomy ushers in more aggressive
surgical approaches for cancer
Baltimore surgeon William Halsted
pioneers a new approach to removing breast
tumors, radical mastectomy, in which the entire
breast and the surrounding lymph nodes and
chest muscles are removed. This helps reduce
recurrences of the disease, which was previously
nearly always fatal.
Halsted’s work also leads to similar approaches
for other cancers, in which both the tumor and
surrounding tissue are removed. These
techniques are still an important part of treatment
for some cancers today. For breast cancer,
however, surgeries have become far more
conservative and effective, enabling many
women to avoid mastectomy altogether.
Steven Paget proposed his "seed and soil"
theory of cancer. He analyzed over 1000
autopsy records of women who had breast
cancer and found that the patterns of
metastasis were not random. Thus, he
proposed that tumor cells (the seeds) have a
specific affinity for specific organs (the soil),
and metastasis would only result if the seed
and soil were compatible.
Bacterial toxins linked to cancer treatment,
presaging BCG in Bladder cancer prevention.
1896 a German Physics Professor
Wilhelm Conrad Roentgen used the term
‘X-ray’ during a lecture he gave (X is the
algebraic symbol of an unknown). Within
months, systems were being devised to use
X-rays for diagnosis. Roentgen won the
first Nobel Prize in Physics for his
In 1896, Beatson presaged moleculartargeted hormonal prevention of breast
cancer by observing that oophorectomy had
a beneficial effect on advanced breast
Removal of the ovaries is performed for the
first time to treat breast cancer.
Marie and Pierre Curie discover radium and later use it to treat tumors.
Tage Anton Ultimus Sjogren was the first to successfully treat cancer
Thor Stenbeck cures a patient with
skin cancer using small doses of daily
radiation therapy. This technique is later
referred to as fractionated radiation
First use of radiation to treat cancer
Five years after Marie Curie’s discovery of radium, doctors report
the first successful of use of this radioactive element to treat cancer, in
two Russian patients with skin cancer. In the following decades, radiation
becomes widely used to treat many different cancers, including cervical,
prostate, breast and other tumors.
In these first decades, doctors use an approach known as brachytherapy,
in which small pieces of radioactive material are implanted inside or next
to tumors, delivering radiation to cancer cells at close range.
Brachytherapy remains an essential part of cancer treatment today, but
has been refined to more precisely target tumor cells while leaving
healthy tissue unharmed.
Discovery of human papillomavirus (HPV)
development occurred in the early 1910s
when George Clowes of Roswell Park
Memorial Institute (RPMI) in Buffalo, New
York, Roswell Park Memorial Institute
developed the first transplantable tumor
systems in rodents.
Francis Peyton Rous provided scientific
backing to the Viral Theory of Cancer by
injecting chickens with cell free liquids
obtained from chicken sarcomas and
observing the formation of sarcomas in the
Theodor Boveri proposed the
Somatic Mutation Theory of Cancer.
He believed that cancer was caused by
Cancer induced in lab animals:
Cancer was induced in laboratory animals for the first time at
Tokyo University, by applying coal tar onto the skin of rabbits, leading
the way for current cancer research methods
Wolbach and Howe reported that
epithelial tissues of rats acquired
neoplastic properties following the
deprivation of fat-soluble vitamin A and
that study of the reverse changes that
follow in the rapid amelioration when the
rats are restored to an adequate diet has
Johannes Fibiger, the Nobel Prize was
awarded to Johannes Andreas Grib Fibiger for
his work that showed a type of worm
(nematode) caused cancer in mice. His
findings were unable to be replicated by other
scientists and were later discredited.
In 1928, Papanicolaou published results of his
study of normal and malignant cytology in
vaginal samples of cells shed from the cervix,
vagina and endometrium in humans.
Named after him, the Pap test was validated
as a diagnostic tool.
In 1932–33, Lacassagne reported
that estrogen could induce mammary
tumors in mice and speculated that
estrogen antagonism (which did not
exist at the time) may prevent breast
First successful pneumonectomy: (surgical
removal of all or part of the lung) for
carcinoma of the lung was performed by
Evarts Ambrose Graham and Jacob Jesse
The first published report of BCG as a cancer vaccine (in Swedish
patients) came out in 1935.
Folic acid was first synthesized in 1937. It was later shown that folate
deficiency could produce a bone marrow picture reminiscent of the effects
of nitrogen mustard.
Farber, Heinle, and Welch tested folic acid in leukemia and they came to
the conclusion that it actually accelerated leukemia cell growth. Although
this observation was later proved to be spurious, Farber collaborated with
Harriet Kilte of Lederle Laboratories to develop a series of folic acid
analogues, which were in fact folate antagonists, and these compounds
included aminopterin and amethopterin, now better known as
Charles Brendon Huggins, discovered that
hormones were necessary for the growth of
certain cancers through his research on
androgen levels and prostate cancer in dogs.
This laid the groundwork for hormone
therapy for certain cancers.
Huggins (AACR president in 1948–
1949) presaged molecular targeted
hormonal prevention of prostate cancer in
a report published by Cancer Research
showing that castration had a beneficial
effect on metastatic prostate cancer,
receiving a 1966 Nobel Prize in
Physiology or Medicine related to this
“Clinical COX-2 targeting in familial
adenomatous polyposis (FAP) and
sporadic colorectal adenoma patients was
based in part on two important laboratory
Louis Goodman and Alferd Gilman use
nitrogen musturd to treat patient with
demonstrate for the first time that
Introduction of Pap test leads to dramatic declines in cervical
The Pap test, named for its inventor, George Papanicolaou,
enables doctors to detect and treat cervical cancers or pre-cancers
before they have a chance to spread. Since the 1950s, widespread use
of the Pap test has helped to reduce U.S. cervical cancer death rates by
nearly 70 percent. Yet cervical cancer remains a major cause of cancer
death in developing countries, where access to screening and treatment
The first electron linear accelerator is designed for radiation
therapy. Today, it is widely used for treatment of cancer.
Bloch and Edward Purcell
discover nuclear magnetic resonance used today to detect brain tumors and
Louis Goodman, who studied chemical warfare
agents during World War II, discovered that
nitrogen mustards could be used in the
treatment of cancer. He published the first paper
reporting the use of nitrogen mustards as the
first chemotherapeutic agents against Hodgkin's
Disease, lymphosarcoma, and leukemias
First-ever remission of pediatric
Sidney Farber, a physician at Children’s
Hospital Boston, achieves the first partial
remission of pediatric leukemia in a 4-year-old
girl using the drug aminopterin. He soon
documents 10 cases of remission in a landmark
scientific paper. Until this time, children with
acute leukemia usually died within weeks of
being diagnosed. While early remissions prove
temporary, they pave the way for therapies that
cure thousands of patients in the decades to
come, allowing most childhood cancer patients
to live long, healthy lives.
Syndey Farber uses Antifolates to
succesfully induce remission in
children with acute lymphoblastic
George Hitchings and Gertude
Elion isolated a substance
inhibited adenine metabolism.
First chemotherapy drug approved for cancer
Following results of clinical trials conducted in 1946 and 1947,
nitrogen mustard is approved by the Food and Drug Administration
(FDA) for the treatment of Hodgkin lymphoma. Nitrogen mustard –
also known as mustard gas and stockpiled as a weapon in World War II
kills cancer cells by modifying their DNA through a process called
alkylation. Its discovery spurs rapid advancements in chemotherapy,
and the drug still receives some use today in combination
chemotherapy for Hodgkin lymphoma.
1950s – 1960s
The antibiotic, actinomycin D had significant antitumor properties and enjoyed
considerable use in pediatric tumors in the 1950s and 1960s. This drug
established the initial interest in the search for more active antitumor
antibiotics, and this effort yielded a series of active antitumor antibiotics in
common use today.
Smoking linked to cancer; cessation campaigns begin
In the 1950s, studies begin to show that smoking is a major cause of cancer,
particularly lung cancer. In the early 1960s, both the U.S. Surgeon General and the
U.K. Royal College of Physicians issue reports linking smoking to cancer and other
serious health problems. In later years, smoking is also established as a major cause of
pancreatic cancer, and second-hand smoke is declared a threat to the health of nonsmokers. Tobacco control and smoking cessation soon become the most important
strategies for reducing the worldwide toll of lung cancer .
Leborgne classified breast microcancer in 1950, followed by the first
equipment dedicated to mammography in1956.
George Hitchings and Gertude Elion they had developed two drugs
that would later play an important role in the treatment of acute
Development of mechlorethamine (Mustargen) and chlorambucil.
Slaughter and colleagues helped clarify carcinogenesis in the oral
cavity and other epithelial sites with their report of the concept “ field
Auerbach began (in the lung) some of the first detailed histologic
studies of multistep progression (from hyperplasia to metaplasia to
dysplasia to carcinoma in situ to cancer), which correlated with
intensity of smoking.
Charles Heidelberger and colleagues at the
University of Wisconsin developed a drug that was
aimed at nonhematologic cancers .
They identified a unique biochemical feature of rat
hepatoma metabolism in that there was greater
uptake and use of uracil relative to normal tissue.
Based on this observation, Heidelberger ‘‘targeted’’
this biochemical pathway by attaching a fluorine
atom to the 5-position of the uracil pyrimidine
base, which resulted in the synthesis of the
fluoropyrimidine 5- fluorouracil (5-FU).
This agent was found to have broad-spectrum
activity against a range of solid tumors and, to this
day, remains the cornerstone for the treatment of
Henry Kaplan is the first physician in the
Western hemisphere to use the linear accelerator
to treat retinoblastoma, an incurable eye cancer.
This technology is now used worldwide to treat
Hodgkin's disease and other forms of cancer.
Approval of Methotrexate in Choriocarcinoma
Roy Hertz and Min Chiu Li demonstrated that as a single agent can
cure choriocarcinoma, the first solid tumor to be cured by
Pioneering “combination chemotherapy” cures leukemia
NCI scientists demonstrate that combination chemotherapy in which
multiple drugs are administered together can cause remissions in both
children and adults with acute leukemia. Their findings set the stage for
nearly all modern chemotherapy, in which drug combinations, dosing
and scheduling have been carefully refined to maximize effectiveness
while minimizing side effects.
The Food and Drug Administration (FDA) approved the alkylating
Howard Temin proposed the DNA Provirus
Hypothesis of cancer. This asserts that certain
RNA viruses are capable of inserting their
genetic material into the DNA of the host cells.
These inactive proviruses can eventually be
expressed and may contribute to the formation
Saul Rosenberg, Henry Kaplan, and their
colleagues begin to develop combined
modality therapy - combining drugs,
radiation, and surgery - that has dramatically
improved survival rates for patients with
Researchers link “Philadelphia chromosome” to leukemia
Investigators in Philadelphia identify a chromosomal
abnormality linked to many leukemias. A decade later, researchers
discover that this abnormality results when parts of two
chromosomes –chromosomes 9 and 22 – switch places in a
phenomenon called translocation. It later becomes the target of one
of the first-ever targeted cancer treatments, Imatinib (Gleevec),
which transforms treatment of chronic myelogenous leukemia and
Lars Leksell develops the
radiosurgical tool that uses a
high dose of radiation to
eradicate cancerous cells.
Malcolm Bagshaw develops a type of
radiation therapy called high-dose, small-field
radiation to treat prostate cancer without the
need for surgery.
Discovery of Vinca Alkaloids i.e. Vincristine and Vinblastine at the
Eli Lilly Company.
Discovery of the activity of ibenzmethyzin in Hodgkin’s disease (soon
to be renamed procarbazine) by Brunner and Young and DeVita and
The Epstein-Barr virus is linked to human cancer for the first time.
• Combination chemotheraphy (POMP regimn) is able to induce long
term remission in children with ALL.
• Chemotherapy found to cure Hodgkin lymphoma
Researchers led by Vincent De Vita discover that a new
chemotherapy regimen called MOPP (mechlorethamine, vincristine,
procarbazine and prednisone) cures up to 50 percent of patients with
advanced Hodgkin lymphoma. This regimen quickly becomes the
• In the 1970s, a different chemotherapy combination (doxorubicin,
bleomycin, vinblastine and dacarbazine – known as ABVD) proves
even more effective, curing about 70 percent of patients with advanced
Hodgkin lymphoma. The ABVD combination remains a mainstay of
Discovery of Estrogen receptor by Elwood
In 1966, Wattenberg (AACR president in
1992–1993) introduced the term
‘‘chemoprophylaxis’’ in a landmark review
of experimental inhibition of chemically
induced animal carcinogenesis that
appeared in the AACR journal Cancer
Blumberg had discovered the hepatitis B virus in 1967 and its link
with hepatocellular carcinoma in 1975.
Bollag began a program to synthesize the first analogues of vitamin A,
later coined as “retinoids” by sporn. He hypothesized that these
analogues not only would enhance potential therapeutic and preventive
effects of natural vitamin A but also would reduce its well-known
severe toxicity (hypervitaminosis A).
Arthur Kornberg synthesizes
biologically active DNA in a test tube,
spurring development of engineering
techniques in medicine and
Late 1960s – early 1970s
Screening tests for colorectal cancer dramatically reduce deaths
In 1967, the guaiac fecal occult blood test (FOBT) is introduced
as a screening test for colorectal cancer, one of the most common forms
Within the next few years, two new screening techniques –
flexible sigmoidoscopy and colonoscopy enable physicians to examine
the colon using a small camera attached to a flexible lighted tube.
The widespread use of these approaches leads to better detection
of precancerous polyps and early stage cancers that are usually curable
Increased use of radioactive “seeds” to target prostate and
In this approach, tiny radioactive sources or “seeds” are implanted
directly into the prostate gland, delivering a high dose of radiation
directly to the tumor while leaving healthy tissue beyond the prostate
Brachytherapy has been used since the early 1900s, but became
less common after the widespread adoption of external beam radiation.
With refined techniques and conclusive data on its effectiveness, the
approach once again becomes a central part of treatment for prostate,
cervical and other cancers.
CT scanning provides clearer images of tumors, guiding
radiation and other treatments
Researchers perform the first computed tomography (CT) scan
on a human patient a woman with a suspected brain tumor. CT
scanning uses X-rays to create images or “slices” of the brain,
allowing doctors for the first time to clearly see tumors arising in the
soft tissue of the brain. Over the following decades, CT scanning
enables doctors to assess the size, shape and location of many other
types of tumors, and to carefully target radiation and surgery to hit
the tumors without harming healthy tissue.
Leonard Herzenberg develops the flourescenceactivated cell sorter, revolutionizing the study of
Vinvcet Devita and colleagues cure lymphomas
with combination chemotherapy.
More limited mastectomy proven effective for early-stage breast
While radical surgery had been routinely used to treat breast
cancer, a more limited surgical procedure called total mastectomy
(removing just the breast tissue instead of removing the breast, chest
wall muscle and underarm lymph nodes) is confirmed to be as effective
for women with early-stage breast cancer. The procedure reduces pain
after surgery and speeds recovery for patients. This advance paves the
way for future breast-conserving surgeries.
Emil Frei and colleagues demonstrate
that chemotherapy given after surgical
removal of osteosarcoma can improve
cure rates. (Adjuvant Chemotherapy)
William Robinson isolates the genome of
the virus that causes hepatitis B and a
common form of liver cancer.
Zur Hausen reported the link between
HPV infection and cervical cancer.
Jordan showed that the selective estrogen
receptor modulator (SERM) tamoxifen
prevented mammary tumors in rats.
Dr. Lawrence Einhorn finds a cure for
advanced testicular cancer. This
changes the cure rate from 5 percent
to 60 percent.
A combination of Cyclophosphamide, methotrexate and fluorouracil (CMF)
was shown to be effective as adjuvant treatment for node-positive breast cancer.
First adjuvant chemotherapy increases cure rates for early-stage breast
After overcoming concerns in the cancer community about whether the
benefits outweigh the risks, Dr. Bernard Fisher and Gianni Bonadonna
demonstrate that chemotherapy after surgery known as adjuvant chemotherapy
prolongs the lives of women with early stage breast cancer. Their studies
involve use of the drugs l-phenylalanine mustard or a combination of
cyclophosphamide (Cytoxan), methotrexate and fluorouracil. Adjuvant
chemotherapy becomes a major component of treatment for the disease,
improving survival and cure rates in the years ahead.
Scientists Georges Kohler and
Cesar Milstein develop tailormade antibodies in large
quantities in a laboratory,
leading to ways of attacking
cancer and diagnosing disease.
They go on to win the Nobel
Prize in 1984.
Harold E. Varmus and J. Michael Bishop
discovered the first cellular oncogene,. a gene
that, when mutated or expressed at high levels,
helps turn a normal cell into a cancer cell. They
win the 1989 Nobel Prize. This is the same gene
carried by the virus originally described by
In 1976, Weinstein (AACR president in 1990–
1991) and collaborators reported key early
studies of the carcinogen benzo(a)pyrene that
led to the broad study of DNA adducts in
polycyclic hydrocarbons and other carcinogens
such as aflatoxins.
New treatments cure men with testicular cancer
A pivotal trial shows that combining the drugs cisplatin, vinblastine
(Velban, Velsar) and bleomycin (Blenoxane) can cure 70 percent of
patients with advanced testicular cancer. Cisplatin is approved by the FDA
the following year. Today, the overall cure rate for testicular cancer (all
stages) is a remarkable 95 %. In recent years, the cyclist Lance
Armstrong’s high-profile diagnosis, treatment and recovery from the
disease – and his subsequent Tour de France victories – have brought new
attention to these advances, and to the vital role of clinical trials in
progress against cancer.
The FDA approves cisplatin for the treatment of ovarian cancer, a drug
that would prove to have activity across a broad range of solid tumors.
Growing use of mammography saves lives
Regular breast cancer screening with mammography becomes
increasingly common, helping to detect cancers at an earlier, more
treatable stage. By the mid-1980s, nearly one-third of U.S. women over
age 40 are screened.
By 2008, the proportion screened approaches 70 percent. High
screening rates and resulting early detection have contributed to a 27%
reduction in breast cancer mortality among U.S. women since 1975.
First cancer vaccine prevents cancer-causing hepatitis B infection
The FDA approves the first vaccine against hepatitis B, one of the
primary causes of liver cancer.
In 1991, the U.S. begins routine vaccination of all children against
hepatitis B, and by 2007, the number of acute hepatitis B cases among
children under 15 years declines by 98%.
Limited surgery helps rectal cancer patients avoid
A new procedure called total mesorectal excision emerges as a
new standard surgical treatment for many patients with rectal cancer.
The procedure involves removing only the cancerous region of the
rectum, allowing patients to maintain normal bowel function.
In 1983, Vogelstein reported early cancer related epigenetics data
showing that hypomethylation occurs in premalignancy.
Zur Hausen discovered the first specific human HPV (type 16) in
cervical cancer patients in 1983, leading to an RCT of an HPV-16
vaccine developed by Lowy, Schiller, and others and then to RCTs
begun in 1991 to test quadrivalent and bivalent HPV vaccination for
preventing cervical cancer in girls and young women.
Mark Davis and Tak Mak (Ontario Cancer
Institute) isolate gene coding for part of the T cell
receptor, a key to the immune system's functions.
The discovery brings scientists closer to the goal
of developing vaccines to fight cancer.
J. Martin Brown develops the drug
tirapazamine to attack the hypoxic cells in solid
tumors, offering hope for the treatment of
cervical, breast, headn and neck and prostate
Jeffery Sklar, Michael Cleary (pictured), and
fellow Stanford scientists use purified genetic
probes to diagnose cancer.
• Stephen H. Friend et al., isolated the first tumor suppressor gene, Rb (for
retinoblastoma).This gene was also one of the first associated with an
inherited (familial) form of cancer.
• PSA test enables early detection of prostate cancer
The FDA approves the first PSA (prostate-specific antigen) test to
screen for prostate cancer – the most common form of cancer in men aged
50 and older.
• Second-hand smoke formally declared a carcinogen
The U.S. Surgeon General, and later the International Agency for
Research on Cancer, officially state that second-hand smoke is a
carcinogen. A number of cities around the world ban indoor smoking in
the years that follow.
• Tamoxifen reduces breast cancer recurrence
Tamoxifen (Novaldex) is approved as adjuvant therapy for
post-menopausal women following breast cancer surgery.
Irving Weissman uses cell separation techniques to
isolate pure blood-forming stem cells in mice.
In 1991, he separates these stem cells from human
bone marrow cells, offering promise for the
treatment of leukemias and breast cancer.
• The NCI introduces disease oriented screening using 60 cell lines
derived from different types of human tumor.
• Drugs to boost blood cells help patients finish cancer treatment,
The FDA approves the drug epoetin alpha (Procrit, Epogen) to
stimulate production of red blood cells in patients with severe anemia,
one of the most common and serious side effects of chemotherapy.
These drugs are soon joined by white blood cell-boosting drugs
such as filgrastim (Neupogen) and pegfilgrastim (Neulasta). The new
treatments help reduce the need for blood transfusions and make
chemotherapy safer by reducing the risk of infections and related
Adjuvant therapy proven for colorectal cancer
Pivotal clinical trials show that chemotherapy following surgery
(adjuvant treatment) in patients with stage III colorectal cancer reduces
the risk of cancer recurrence by about 40%.
Later refinements using newer drugs, radiation and sophisticated
treatment schedules help to lower recurrence rates even further.
Together with greater screening to detect colon cancer early, adjuvant
therapy has contributed to a 40% reduction in colon cancer mortality in
the U.S. since the 1970s.
Benzene discovered to cause blood cancers
Scientists find that occupational exposure to benzene, a
chemical commonly used as a solvent and in oil-related products,
is associated with increased risk of developing non-lymphocytic
leukemia, non- Hodgkin lymphoma, and other diseases.
Following this discovery, workers begin taking steps to protect
themselves from benzene exposure and reduce their cancer risk.
Laparoscopic surgery minimizes pain, recovery time for
Beginning in the 1990s, laparoscopic surgery in which a
surgeon makes several small incisions and uses telescoping
equipment to remove tumors emerges as an alternative to
traditional open surgery for some cancers, including kidney,
prostate and colorectal cancer. This new approach allows patients
to recover faster and experience less pain, without sacrificing
Shift to 3-D radiation treatment plans increases precision,
safety of therapy
Thanks to the integration of powerful computers into medicine,
doctors are able to dramatically improve radiation therapy by
creating 3-D treatment plans. These plans require highly complex
calculations and vastly more computing power than earlier, twodimensional treatment plans. Thanks to this advance, radiation can be
targeted at tumors from multiple angles, with beams of varying
power, in ways that minimize the damage to healthy, surrounding
The FDA approved BCG for preventing recurrence of superficial
bladder cancer in 1990 based on several clinical trials including one by
the Southwest Oncology Group.
Recognition of H. pylori as the major worldwide cause of stomach cancer
followed the 1989 and 1991 discovery by Blaser and others of its link with
Powerful anti-nausea drugs alleviate major side effect of cancer treatment
Ondansetron (Zofran) is approved by the FDA to prevent vomiting
caused by chemotherapy and/or radiation. The drug works by deactivating the
nervous system’s natural trigger for vomiting.
Other, similar drugs are soon approved, including granisetron (Kytril),
dolasetron (Anzemet) and palonosetron (Aloxi).
These and other anti-nausea drugs, like aprepitant (Emend), make it
possible for most cancer patients to receive chemotherapy in an outpatient
setting, with minimal disruption to their daily routines.
The U.S. Human Genome project begins. The first gene transfers in
humans also take place in that same year
• Susan Knox uses radiolabeled monoclonal antibodies to treat
patients with lymphoma and solid tumors.
• Ronald Levy develops customized cancer vaccine to trigger anti-
tumor activity by the immune systems of non-Hodgkin's lymphoma
FDA approved Paclitaxel (Taxol) which becomes the first
‘blockbuster’ oncology drug.
Sentinel lymph node biopsy determines cancer’s spread with fewer
Sentinel lymph node biopsy becomes a less invasive way to
assess whether cancer has spread in patients with early-stage
melanoma, the most aggressive form of skin cancer.
The procedure involves surgically removing the lymph node
closest to the primary tumor – the “sentinel” node and examining it
under a microscope for evidence of cancer. If the sentinel node is
cancer-free, no further lymph nodes are removed and the patient is
spared the previous practice of removing a large number of nodes.
This allows for easier recovery and reduces the risk of
postoperative side effects such as lymphedema, a painful swelling of
the extremities. Sentinel lymph node biopsy is later found to be
effective for women with breast cancer.
Branimir Sikic develops new approaches to overcome multi-drug
resistance in cancer cells, enhancing the ability of chemotherapeutic
drugs to treat leukemia, lymphoma and solid tumors.
Robert Negrin, Samuel Strober, and Edgar Engleman develop and
initiate stem-cell transplants, which are less invasive, less costly, and
more effective than transplantation of bone marrow.
DuBois (AACR president in 2008 – 2009) and colleagues showed in
1994 that COX-2 is up-regulated in human colorectal adenomas and
In 1994, investigators reported the first systematic study of methylation
as a very early event of human colorectal neoplasia.
First DNA microarray chip was constructed and used to measure gene
expression levels in plants. This technology has been advanced and is
now used to study cancer in humans. Currently 'gene chips' are being
investigated as tools in the development of individualized treatment
Investigators showed that targeting to reverse methylation can prevent
intestinal neoplasia in mice.
Taketo and colleagues showed COX-2 targeting was effective against
intestinal neoplasia in adenomatous polyposis coli (Apc) knockout
In 1997, an inverse association between H. pylori and gastroesophageal
junction adenocarcinoma was reported.
• FDA approves first-ever targeted cancer drug, Rituximab
The FDA approves the first molecularly targeted cancer drug,
rituximab (Rituxan), to treat patients with B-cell non-Hodgkin’s
lymphoma who no longer respond to other treatments.
Rituximab is in a new class of drugs called monoclonal antibodies,
and targets a protein on the surface of immune cells known as B cells,
interfering with the development of cancer. It is later combined with
other cancer therapies to boost cure rates and increase survival.
Surgery found to cure some patients with advanced colon cancer
In general, metastatic cancer is difficult or impossible to treat
with surgery because tumor cells are spread throughout the body. But
in 1997, researchers find that some colon cancer patients whose cancer
has metastasized to the liver only can be cured with surgery.
In a study of nearly 300 such patients who underwent surgery
between 1960 and 1987, about one in four were still alive five years
later, and nearly of all of these patients were found to have been
A later study finds that use of positron emission tomography, or
PET scanning, can identify some liver metastases that would have gone
unnoticed before, helping surgeons in the study to achieve a cure rate
Drug therapy can reduce breast cancer risk in women at high risk
The FDA approves Tamoxifen (Novaldex), a hormonal drug already
used to prevent recurrence of breast cancer, to reduce the risk of
developing breast cancer in women who are at high risk for the disease.
The approval is based on a large trial showing that tamoxifen reduced
breast cancer risk by more than 40 percent in women with a strong family
history of breast cancer or with mutations in the BRCA1 and BRCA2
In 1998, the FDA approved Valrubicin for preventing BCG-refractory
superficial bladder tumor recurrence.
Chemotherapy before surgery helps more women benefit from
A major trial reports that an approach called neoadjuvant
chemotherapy providing chemotherapy before surgery allows more
than two-thirds of women with large breast tumors to undergo breast
conserving surgery called lumpectomy, instead of full mastectomy.
Neoadjuvant therapy is later shown to benefit patients with rectal
and other cancers.
First successful creation of tumor cells
Human epithelial and fibroblast cells were transformed into tumor
cells for the first time in a laboratory. This was accomplished by the coexpression of telomerase(hTERT), the simian virus 40 large-T
oncoprotein, and an oncogenic allele of H-ras.
Prophylactic surgery helps prevent breast and ovarian
cancers in women at high risk
A major review of published studies confirms that removal
of the ovaries and fallopian tubes in premenopausal women with
BRCA mutations reduces the risk of breast cancer by 51 percent
and the risk of ovarian and fallopian tube cancers by 79 %.
New radiotherapy technique enables precise targeting of tumors
near sensitive tissue
Doctors begin using intensity modulated radiation therapy (IMRT),
a highly advanced radiation technique, to precisely target tumors that lie
close to vital organs and other sensitive tissue that must be protected
from radiation. IMRT allows doctors to minimize radiation exposure to
the spinal cord, optic nerve and salivary glands, reducing side effects
without compromising tumor control.
Study links household radon exposure to lung cancer
The Iowa Radon Lung Cancer Study demonstrates that
ongoing exposure to residential radon – a naturally-occurring radioactive gas
that can emerge through basements and crawl spaces is associated with
increased risk of lung cancer.
The Environmental Protection Agency now estimates that more
than 20,000 lung cancer cases in the U.S. are due to long-term radon exposure
in the home. Since the study, radon inspections have become a routine part of
homeownership, promising to reduce the future burden of the disease.
Studies by Brain Druker lead to FDA approval of Imatinib mesylate
(Glivec) for chronic myelogenous leukemia, a new paradigm for
targeted therapy in oncology.
Branimir Sikic , George Fisher, and Cheryl Cho develop a new
treatment for metastatic colorectal cancers using an inhibitor of
epidermal growth factor receptor in combination with chemotherapy, the
Scientists decode the human genome
Scientists announce that they have successfully mapped the 3
billion DNA letters in the human genome. This marks the completion of
the Human Genome Project, an unprecedented international
collaboration between researchers in the U.S. in and six other countries,
funded primarily by the U.S. government.
Results of the 13-year effort are made freely available to scientists
around the world, paving the way for research to identify the genetic
defects that fuel cancer, and for new ways of screening for and treating
First targeted drugs for lung cancer attack “EGFR” receptor
The FDA approves two new targeted treatments for advanced, non-small
cell lung cancer, Gefitinib (Iressa) and Erlotinib (Tarceva).
Both drugs target the epidermal growth factor receptor (EGFR), a
protein on cell surfaces that is involved in driving lung cancer growth and
Reported in 2003, the other major advance with molecular targeted hormonal
cancer prevention was the large-scale PCPT of the 5α-reductase inhibitor
(type 2) finasteride, which blocks production of potently carcinogenic
dihydrotestosterone. Although finasteride significantly reduced prostate cancer
risk in PCPT, its acceptance for this use has been blocked by concerns that
finasteride increased high-grade prostate cancer and only prevented clinically
• The FDA approves Bevacizumab (Avastin), the first clinically proven
anti-angiogenic agent, for the treatment of colon cancer.
• Researchers at Harvard university define mutations in the epidermal
growth factor receptor that confer selective responsiveness to be
targeted agent Gefitinib, indicating that molecular testing might be
able to prospectively identify subsets of patients that will respond to
Two targeted drugs approved for advanced colon cancer
The drugs Cetuximab (Erbitux) and Panitumumab
(Vectibix) are approved to treat colon cancer that has spread to other
parts of the body (metastatic disease).
These drugs attack tumors that express the epidermal
growth factor receptor (EGFR) protein, which is involved in cancer
cell growth. Later, a coordinated analysis of multiple studies shows that
cetuximab and panitumumab are effective only in patients with the
normal form of a gene known as KRAS. This discovery helps
physicians ensure that the drugs are used only for patients who stand to
benefit, while eliminating unnecessary treatment and costs for patients
who will not.
First targeted anti-breast cancer drug, Trastuzumab (Herceptin), has major
impact on care
The FDA approves the groundbreaking drug Trastuzumab (Herceptin)
after research shows that adding the monoclonal antibody to chemotherapy
dramatically increases survival for women with advanced breast cancer that
over-produces a protein called HER2.
In 2006, the drug is also approved as part of adjuvant therapy (after
surgery) for women with early-stage HER2-positive breast cancer, after two
major trials show that it reduces the risk of recurrence by more than 50 percent,
an unprecedented result.
About 25 %of breast cancer patients have HER2-positive disease, and
prior to the introduction of trastuzumab, there were no effective treatments for
these cancers, which were considered some of the most aggressive, deadly
forms of the disease.
Recently, trastuzumab was also FDA-approved to treat patients with
stomach cancers that have a similar over-production of the HER2 protein.
First vaccine approved to prevent cervical cancer
The FDA approves the first vaccine to prevent infection with two highrisk strains of the human papillomavirus (HPV16 and HPV18) that are known
to cause about 70% of all cervical cancers.
The vaccine, called Gardasil, is approved for girls and young women
aged 9 to 26, based on a clinical trial showing that the vaccine was safe and
was 100 percent effective against these types of HPV, and those that cause
genital warts, for at least four and a half years after vaccination.
A second vaccine, Cervarix, is approved in 2009 to prevent infection
against the cancer-causing HPV strains in young women aged 10 to 25.
Gardasil is later approved to prevent additional HPV-related diseases in
children and young adults aged 9 to 26, including vaginal, vulvar and anal
cancers in females, and anal cancer and genital warts in males. Studies have
also linked HPV infection to head and neck cancers, suggesting that the vaccine
may help prevent these cancers as well.
The FDA approves Nexavar, an oral inhibitor for liver cancer.
This is the only drug approved for liver cancer.
German scientist Harald zur Hausen
wins a Nobel Prize for his research
that found that oncogenic human
papilloma virus or HPV, causes
cervical cancer, the second most
common cancer among women.
He made the discovery in the
Reported in 2009, the related Reduction by Dutasteride of Prostate
Cancer Events (REDUCE) trial of the dual (type 1 and type 2) 5αreductase inhibitor Dutasteride found that prostate cancer risk went
down by 23% and high-grade prostate cancer did not increase
significantly (versus placebo) in a higher-risk group (e.g., elevated
prostatespecific antigen, albeit with a prior negative biopsy) than that
of PCPT. These results confirm a class effect of 5α-reductase inhibitors
and have important regulatory implications for prostate cancer
CT scanning reduces lung cancer deaths among heavy smokers
Initial results from a large clinical trial involving more than
50,000 participants shows that that annual screening with low-dose
spiral CT (LDCT) scans can reduce the risk of lung cancer death by 20
percent in current and former heavy smokers.
The National Lung Screening Trial, funded by the National
Cancer Institute, compared CT scanning to chest X-rays in this group
of people at high risk for developing lung cancer.
This finding marks the first-ever lung cancer screening approach
that has been shown to reduce lung cancer mortality. The debate about
the appropriate use of CT screening among the general population,
First drug shown to improve survival for patients with advanced
The targeted drug Ipilimumab (Yervoy) is found to significantly
improve survival in a select group of patients with advanced melanoma who
have undergone previous therapy, compared to those treated with a form of
vaccine therapy that was comparable to placebo.
Ipilimumab is a type of targeted drug known as a monoclonal
antibody, which works by targeting key molecular pathways to enhance the
immune system’s ability to fight cancer. The drug was approved in early
2011, offering new hope to many patients with this hard-to-treat cancer.
Adding palliative care to standard chemotherapy improves survival for
advanced lung cancer patients
A head-to-head trial shows that patients who received standard
chemotherapy along with palliative care (specialized treatment to address the
symptoms of cancer, but not treat the disease) immediately after their diagnosis
with advanced lung cancer lived three months longer and had a higher quality
of life than patients who had chemotherapy alone.
Patients who received the combination approach were also less likely to
undergo aggressive therapy at the end of life, such as resuscitation. The results
demonstrate the potential for palliative care to no only improve quality of life,
but to extend patients lives as well.
First sequencing of multiple myeloma genome
A team of scientists including Rafael Fonseca, William C. Hahn,
Matthew Meyerson, and Todd R. Golub reported the first-ever
sequencing of genomes from 38 patient samples of multiple myeloma,
a type of blood cancer. The study revealed new and unexpected genetic
mutations affecting certain pathways, such as NF-κB signaling and the
kinase BRAF, as well as mutations in genes regulating RNA
processing, protein folding, and blood coagulation. These findings give
further insight into the disease. Identification of the link between
BRAF and multiple myeloma will likely lead to clinical studies
evaluating existing targeted drugs (BRAF inhibitors) for treatment of
New Techniques to view the Process in Living Cells
L. Stirling Churchman of the University of California, San
Francisco, developed a new technique that allows the process of
transcription (how the cell makes RNA from the DNA template) to be
studied in living cells at high resolution. Using this technology,
researchers will now be able to watch transcription as it is happening,
leading to important insights into how genes are turned on and off.
This is likely to have implications for the understanding of normal
development as well as of cancer and other diseases.
New biomarkers to predict response to therapy in lung cancer
John V. Heymach, Waun Ki Hong and colleagues at The
University of Texas MD Anderson Cancer Center, Houston, reported
the identification of two sets of genes that predict response to
Tarceva/erlotinib, a targeted therapy used for treatment of certain nonsmall cell lung cancers. These gene “signatures” were based on the
results of the BATTLE clinical trial and will have broad significance, as
they will allow physicians to better determine effective treatment
regimens for patients.
Promising target for treatment of non-small cell lung cancer
Nathanael S. Gray, Matthew Meyerson and colleagues at DanaFarber Cancer Institute, Boston, reported that the gene FGFR1 is
amplified in 21% of squamous cell lung cancers. In cell lines,
inhibition of FGFR blocked cell growth. These findings suggest that
FGFR may be a promising therapeutic target for these lung cancers.
Brain cancer stem cell molecule identified
Jeremy N. Rich of Cleveland Clinic, Cleveland, and colleagues,
reported new findings about brain cancer stem cells. Malignant
gliomas, aggressive brain tumors with limited treatment options,
contain highly tumorigenic subpopulations of cancer stem cells. The
researchers identified an enzyme, nitric oxide synthase-2 (NOS2),
required for these stem cells to grow and seed tumors. High NOS2
levels correlate with decreased survival in patients with glioma. Drugs
that block NOS2 slow brain tumor growth in mice. Scientists hope
these findings will enable glioma stem cells to be targeted in humans,
providing an effective new treatment option.
New target for treatment of blood cancers
James E. Bradner of the Dana-Farber Cancer Institute, Boston,
and colleagues, identified the protein Brd4 as a critical requirement for
acute myeloid leukemia (AML) disease maintenance. Brd4 functions
to control expression of Myc, a protein frequently disrupted in many
cancers. Blocking Brd4, using either RNA interference or a drug called
JQ1, led to anti-leukemic effects such as cancer cell death and a delay
in disease progression. These findings were published in the journal
Nature. In a second paper published in the journal Cell, Bradner and
colleagues reported the additional success of JQ1 in stopping the
growth of multiple myeloma cells, which are dependent on Myc. These
studies establish inhibition of Brd4 as a promising therapeutic strategy
in multiple cancers.
Novel mechanism of gene regulation identified
Judith Lieberman of the Immune Disease Institute and Harvard
Medical School, Boston, and colleagues, reported the first description
of competing endogenous RNAs (ceRNAs) and their function.
ceRNAs comprise a complex regulatory network that controls gene
expression through binding of other RNAs called microRNAs. This
study demonstrated that PTEN, a tumor suppressor, is regulated by 150
ceRNAs in human prostate and colon cancer cell lines. A separate
study linked ceRNA-mediated regulation of PTEN to glioblastoma
brain cancer. The discovery provides a new understanding of the
genetics underlying cancer.
Novel gene implicated in adrenal tumors and severe hypertension
Tobias J.E. Carling and colleagues at Yale University School of
Medicine, New Haven, identified novel genetic mutations that can give
rise to tumors of the hormone-producing adrenal gland (Aldosteroneproducing adrenal adenoma) and severe hypertension (high blood
pressure). By sequencing the genes from these tumors and comparing
them to normal DNA, the researchers identified mutations in a
potassium channel gene, KCNJ5. In addition to causing these tumors,
they also found that inherited mutations in KCNJ5 cause a rare familial
form of severe hypertension.
Identification of new oncogene in melanoma
Craig J. Ceol of University of Massachusetts Medical School,
Worcester, and colleagues, reported the identification of the gene
SETDB1 which is capable of accelerating melanoma formation in
zebrafish. SETDB1 cooperates with BRAF(V600E), the most common
mutation in human melanoma; the SETDB1 gene encodes a histone
modifying enzyme often upregulated in those tumors. This finding
supports the model that disruption of histone modification promotes
cancer. SETDB1 may also be a promising drug target.
New technology for identifying and screening cancer biomarkers
Amanda Paulovich, Peter S. Nelson and colleagues at Fred
Hutchinson Cancer Research Center, Seattle, used a highly sensitive
and targeted analytical technology, selected reaction monitoring mass
spectrometry, to test candidate protein biomarkers. This technology
allows highly specific and sensitive measurement of many proteins
from a small drop of blood. The researchers identified those proteins
that were elevated in the blood of mice with breast cancer as compared
to healthy mice. A subset of these proteins were found to be elevated
before tumors could be seen, suggesting that they could be used for
early detection of the cancer. The goal is to apply this strategy to
determine the most promising protein biomarkers associated with early
breast cancer development in humans.
FDA Approval of Brentuximab vendotin (Adcretris) for
Hodgkin lymphoma after failure of autologous stem cell
transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT
candidates and systemic anaplastic large cell lymphoma after
failure of at least one prior multi-agent chemotherapy
FDA Approval of Everolimus (Afinitor) for the treatment of
progressive neuroendocrine tumors of pancreatic origin in
patients with unresectable, locally advanced or metastatic
FDA Approval of Peginterferon alfa-2b (Sylatron) indicated
for the adjuvant treatment of melanoma with microscopic or
gross nodal involvement within 84 days of definitive surgical
resection including complete lymphadenectomy.
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