TIMELINE OF CANCER
Prepared By
Mr. Naveen Kadian
What is Cancer?
 A term for diseases in which abnormal cells divide without control and

can invade nearby tissues. Cance...
Origin of word Cancer
 The origin of the word cancer is credited to the Greek physician

Hippocrates (460-370BC), who use...
3000 B.C.
Evidence of cancer:
 Signs of cancer are found on the bones of mummies from ancient Egypt

and Peru dating back...
Oldest specimens of cancer
(1900 BC to 1500 BC)
Oldest available specimen of a human cancer is found in the
remains of sku...
 One of the earliest human cancers found in the remains of mummies

was a bone cancer suggestive of osteosarcoma.
 Louis...
400 B.C.
 Hippocrates: known today as the father of medicine,

proposed the Humoral Theory of Medicine, which
states that...
168 B.C.
Galen: a Roman physician, was also a
believer in the Humoral Theory of Medicine.
He believed cancer to be curable...
657 A.D.
Paul of Aegina: One of the most
prominent Byzantine physicians, wrote a
seven volume Epitome of Medicine. In his
...
1190
Moses Maimonides: a prominent
physician, scientist, and philosopher,
wrote ten medical treatises. His fifth
treatise ...
1713
Bernardino Ramazzini: noticed the virtual
absence of cervical cancer among nuns, and the
high incidence of breast can...
1727
 In 1727, however, Le Clerc suggested cutting out swellings, polyps,

and tumefactions before they became cancerous.
1761
Giovanni Morgagni began performing
autopsies to relate illness to pathological
findings,. This helped to set a founda...
1775
Percival Pott showed that chimney sweeps
had an occupation-related cancer risk. Soot
that collected under their scrot...
1779
First cancer hospital founded in Reims, France. The hospital was
moved away from the city due to a widespread fear at...
1829
 Joseph Claude Anthelm Recamier was the

first to recognize cancer metastasis. He listed
changes in eating habits as...
1838
 Johannes

Muller , a German
pathologist, published “On the Nature
and Structural Characteristics of
Cancer, and of ...
1846
Advent of general anesthesia opens
the door for modern cancer surgery
In October 1846, a Boston
dentist named William...
1863-1867
R.Virchow, a student of Muller'. He
wrote several papers and a three
volume work, Die krankhaften
Geschwlste, on...
1878
 Theodore

Billroth , a German
surgeon, performed the first pyloric
resection (surgical removal of all or
part of th...
1880s
Radical mastectomy ushers in more aggressive
surgical approaches for cancer
Baltimore surgeon William Halsted
pionee...
1889
Steven Paget proposed his "seed and soil"
theory of cancer. He analyzed over 1000
autopsy records of women who had br...
1893
Bacterial toxins linked to cancer treatment,

presaging BCG in Bladder cancer prevention.
1896
 In

1896 a German Physics Professor
Wilhelm Conrad Roentgen used the term
‘X-ray’ during a lecture he gave (X is th...
1898
 Marie and Pierre Curie discover radium and later use it to treat tumors.
1899
 Tage Anton Ultimus Sjogren was the first to successfully treat cancer

with X-rays.
1900
Thor Stenbeck cures a patient with
skin cancer using small doses of daily
radiation therapy. This technique is later
...
1903
 First use of radiation to treat cancer

Five years after Marie Curie’s discovery of radium, doctors report
the firs...
1907
 Discovery of human papillomavirus (HPV)
1910
A

major
breakthrough
in
model
development occurred in the early 1910s
when George Clowes of Roswell Park
Memorial I...
1914

Theodor Boveri proposed the
Somatic Mutation Theory of Cancer.
He believed that cancer was caused by
abnormal chromo...
1915
 Cancer induced in lab animals:

Cancer was induced in laboratory animals for the first time at
Tokyo University, by...
1925
 Wolbach and Howe reported that
epithelial tissues of rats acquired
neoplastic properties following the
deprivation ...
1926
Johannes Fibiger, the Nobel Prize was
awarded to Johannes Andreas Grib Fibiger for
his work that showed a type of wor...
1928
 In 1928, Papanicolaou published results of his

study of normal and malignant cytology in
vaginal samples of cells ...
1932
 In 1932–33, Lacassagne reported

that estrogen could induce mammary
tumors in mice and speculated that
estrogen ant...
1933
 First successful pneumonectomy: (surgical

removal of all or part of the lung) for
carcinoma of the lung was perfor...
1935
 The first published report of BCG as a cancer vaccine (in Swedish

patients) came out in 1935.
1937
 Folic acid was first synthesized in 1937. It was later shown that folate

deficiency could produce a bone marrow pi...
1939
 Charles Brendon Huggins, discovered that

hormones were necessary for the growth of
certain cancers through his res...
1941
 Huggins (AACR president in 1948–

1949) presaged molecular targeted
hormonal prevention of prostate cancer in
a rep...
1942
 Louis Goodman and Alferd Gilman use

nitrogen musturd to treat patient with
non-Hodgkin’s
lymphoma
and
demonstrate ...
1943
 Introduction of Pap test leads to dramatic declines in cervical

cancer deaths
The Pap test, named for its inventor...
1945
 Felix

Bloch and Edward Purcell
discover nuclear magnetic resonance used today to detect brain tumors and
other can...
1946
 Louis Goodman, who studied chemical warfare

agents during World War II, discovered that
nitrogen mustards could be...
1947
First-ever remission of pediatric
leukemia
Sidney Farber, a physician at Children’s
Hospital Boston, achieves the fir...
1948
 Syndey Farber uses Antifolates to

succesfully induce remission in
children with acute lymphoblastic
leukemia (ALL)...
1949
First chemotherapy drug approved for cancer
Following results of clinical trials conducted in 1946 and 1947,
nitrogen...
1950s – 1960s
 The antibiotic, actinomycin D had significant antitumor properties and enjoyed

considerable use in pediat...
1951
 George Hitchings and Gertude Elion they had developed two drugs

that would later play an important role in the tre...
1952
 Development of mechlorethamine (Mustargen) and chlorambucil.
1953
 Slaughter and colleagues helped clarify carcinogenesis in the oral

cavity and other epithelial sites with their re...
1954
 Auerbach began (in the lung) some of the first detailed histologic
studies of multistep progression (from hyperplas...
Mid 1950s
 Charles Heidelberger and colleagues at the

University of Wisconsin developed a drug that was
aimed at nonhema...
1956
 Henry Kaplan is the first physician in the

Western hemisphere to use the linear accelerator
to treat retinoblastom...
1957
 Approval of Fluorouracil.
1958
 Approval of Methotrexate in Choriocarcinoma
 Roy Hertz and Min Chiu Li demonstrated that as a single agent can

cu...
1959
 The Food and Drug Administration (FDA) approved the alkylating

agent Cyclophosphamide.
1960
Howard Temin proposed the DNA Provirus
Hypothesis of cancer. This asserts that certain
RNA viruses are capable of ins...
Researchers link “Philadelphia chromosome” to leukemia
Investigators in Philadelphia identify a chromosomal
abnormality li...
 Lars Leksell develops the

Gamma
Knife
a
radiosurgical tool that uses a
high dose of radiation to
eradicate cancerous ce...
1962
 Malcolm Bagshaw develops a type of

radiation therapy called high-dose, small-field
radiation to treat prostate can...
1963
 Discovery of Vinca Alkaloids i.e. Vincristine and Vinblastine at the
Eli Lilly Company.
 Discovery of the activity...
1964
 The Epstein-Barr virus is linked to human cancer for the first time.
1965
• Combination chemotheraphy (POMP regimn) is able to induce long

term remission in children with ALL.
• Chemotherapy...
1966
 Discovery of Estrogen receptor by Elwood

V. Jensen
 In 1966, Wattenberg (AACR president in

1992–1993) introduced...
1967
 Blumberg had discovered the hepatitis B virus in 1967 and its link

with hepatocellular carcinoma in 1975.
 Bollag...
1967
 Arthur Kornberg synthesizes

biologically active DNA in a test tube,
spurring development of engineering
techniques...
Late 1960s – early 1970s
Screening tests for colorectal cancer dramatically reduce deaths
In 1967, the guaiac fecal occult...
Early 1970
Increased use of radioactive “seeds” to target prostate and
other cancers
In this approach, tiny radioactive so...
1970’s
CT scanning provides clearer images of tumors, guiding
radiation and other treatments
Researchers perform the first...
1970
Leonard Herzenberg develops the flourescenceactivated cell sorter, revolutionizing the study of
cancer cells.

Vinvce...
1971
More limited mastectomy proven effective for early-stage breast
cancer
While radical surgery had been routinely used ...
1972
 Emil Frei and colleagues demonstrate

that chemotherapy given after surgical
removal of osteosarcoma can improve
cu...
1974
 William Robinson isolates the genome of

the virus that causes hepatitis B and a
common form of liver cancer.
 Zur...
1974
 Dr. Lawrence Einhorn finds a cure for

advanced testicular cancer. This
changes the cure rate from 5 percent
to 60 ...
1975
A combination of Cyclophosphamide, methotrexate and fluorouracil (CMF)
was shown to be effective as adjuvant treatmen...
1975
 Scientists Georges Kohler and

Cesar Milstein develop tailormade antibodies in large
quantities in a laboratory,
le...
1976
 Harold E. Varmus and J. Michael Bishop

discovered the first cellular oncogene,. a gene
that, when mutated or expre...
1977
New treatments cure men with testicular cancer
A pivotal trial shows that combining the drugs cisplatin, vinblastine
...
1978
 The FDA approves cisplatin for the treatment of ovarian cancer, a drug

that would prove to have activity across a ...
Late 1970s
Growing use of mammography saves lives
Regular breast cancer screening with mammography becomes
increasingly co...
1981
First cancer vaccine prevents cancer-causing hepatitis B infection
The FDA approves the first vaccine against hepatit...
1982
Limited surgery helps rectal cancer patients avoid
colostomies
A new procedure called total mesorectal excision emerg...
1983
 In 1983, Vogelstein reported early cancer related epigenetics data

showing that hypomethylation occurs in premalig...
1984
 Mark Davis and Tak Mak (Ontario Cancer

Institute) isolate gene coding for part of the T cell
receptor, a key to th...
1986
• Stephen H. Friend et al., isolated the first tumor suppressor gene, Rb (for

retinoblastoma).This gene was also one...
1986
• Tamoxifen reduces breast cancer recurrence

Tamoxifen (Novaldex) is approved as adjuvant therapy for
post-menopausa...
1988
 Irving Weissman uses cell separation techniques to

isolate pure blood-forming stem cells in mice.
 In 1991, he se...
1989
• The NCI introduces disease oriented screening using 60 cell lines

derived from different types of human tumor.
• D...
1985-1991
Adjuvant therapy proven for colorectal cancer
Pivotal clinical trials show that chemotherapy following surgery
(...
Late 1980s
Benzene discovered to cause blood cancers
Scientists find that occupational exposure to benzene, a
chemical com...
Early 1990s
Laparoscopic surgery minimizes pain, recovery time for
several cancers
Beginning in the 1990s, laparoscopic su...
Early 1990s
Shift to 3-D radiation treatment plans increases precision,
safety of therapy
Thanks to the integration of pow...
1990
 The FDA approved BCG for preventing recurrence of superficial

bladder cancer in 1990 based on several clinical tri...
1991
 Recognition of H. pylori as the major worldwide cause of stomach cancer

followed the 1989 and 1991 discovery by Bl...
1991
 The U.S. Human Genome project begins. The first gene transfers in

humans also take place in that same year
1992
• Susan Knox uses radiolabeled monoclonal antibodies to treat

patients with lymphoma and solid tumors.
• Ronald Levy...
1992
 Sentinel lymph node biopsy determines cancer’s spread with fewer

side effects
Sentinel lymph node biopsy becomes a...
1993
 Branimir Sikic develops new approaches to overcome multi-drug

resistance in cancer cells, enhancing the ability of...
1994
 DuBois (AACR president in 2008 – 2009) and colleagues showed in

1994 that COX-2 is up-regulated in human colorecta...
1995
 First DNA microarray chip was constructed and used to measure gene

expression levels in plants. This technology ha...
1996
 Taketo and colleagues showed COX-2 targeting was effective against

intestinal neoplasia in adenomatous polyposis c...
1997
 In 1997, an inverse association between H. pylori and gastroesophageal

junction adenocarcinoma was reported.
• FDA...
1997
Surgery found to cure some patients with advanced colon cancer
In general, metastatic cancer is difficult or impossib...
1998
 Drug therapy can reduce breast cancer risk in women at high risk

The FDA approves Tamoxifen (Novaldex), a hormonal...
1998
 Chemotherapy before surgery helps more women benefit from

breast-conserving treatment
A major trial reports that a...
1999
 First successful creation of tumor cells

Human epithelial and fibroblast cells were transformed into tumor
cells f...
Late 1990s
Prophylactic surgery helps prevent breast and ovarian
cancers in women at high risk
A major review of published...
Late 1990s
New radiotherapy technique enables precise targeting of tumors
near sensitive tissue
Doctors begin using intens...
2000
 Study links household radon exposure to lung cancer
The Iowa Radon Lung Cancer Study demonstrates that
ongoing expo...
2001
 Studies by Brain Druker lead to FDA approval of Imatinib mesylate

(Glivec) for chronic myelogenous leukemia, a new...
2003
 Branimir Sikic , George Fisher, and Cheryl Cho develop a new

treatment for metastatic colorectal cancers using an ...
2003
 First targeted drugs for lung cancer attack “EGFR” receptor

The FDA approves two new targeted treatments for advan...
2004
• The FDA approves Bevacizumab (Avastin), the first clinically proven

anti-angiogenic agent, for the treatment of co...
2004
 Two targeted drugs approved for advanced colon cancer

The drugs Cetuximab (Erbitux) and Panitumumab
(Vectibix) are...
2006
 First targeted anti-breast cancer drug, Trastuzumab (Herceptin), has major

impact on care
The FDA approves the gro...
2006
 First vaccine approved to prevent cervical cancer

The FDA approves the first vaccine to prevent infection with two...
2007
 The FDA approves Nexavar, an oral inhibitor for liver cancer.

This is the only drug approved for liver cancer.
2008
 German scientist Harald zur Hausen

wins a Nobel Prize for his research
that found that oncogenic human
papilloma v...
2009
 Reported in 2009, the related Reduction by Dutasteride of Prostate

Cancer Events (REDUCE) trial of the dual (type ...
2010
 CT scanning reduces lung cancer deaths among heavy smokers

Initial results from a large clinical trial involving m...
2010
First drug shown to improve survival for patients with advanced
melanoma
The targeted drug Ipilimumab (Yervoy) is fou...
2010
 Adding palliative care to standard chemotherapy improves survival for

advanced lung cancer patients
A head-to-head...
2011
 First sequencing of multiple myeloma genome

A team of scientists including Rafael Fonseca, William C. Hahn,
Matthe...
2011
 New Techniques to view the Process in Living Cells

L. Stirling Churchman of the University of California, San
Fran...
2011
 New biomarkers to predict response to therapy in lung cancer

patients
John V. Heymach, Waun Ki Hong and colleagues...
2011
 Promising target for treatment of non-small cell lung cancer

Nathanael S. Gray, Matthew Meyerson and colleagues at...
2011
 Brain cancer stem cell molecule identified

Jeremy N. Rich of Cleveland Clinic, Cleveland, and colleagues,
reported...
2011
 New target for treatment of blood cancers

James E. Bradner of the Dana-Farber Cancer Institute, Boston,
and collea...
2011
 Novel mechanism of gene regulation identified

Judith Lieberman of the Immune Disease Institute and Harvard
Medical...
2011
 Novel gene implicated in adrenal tumors and severe hypertension

Tobias J.E. Carling and colleagues at Yale Univers...
2011
 Identification of new oncogene in melanoma

Craig J. Ceol of University of Massachusetts Medical School,
Worcester,...
2011
 New technology for identifying and screening cancer biomarkers

Amanda Paulovich, Peter S. Nelson and colleagues at...
2011
 FDA Approval of Brentuximab vendotin (Adcretris) for

Hodgkin lymphoma after failure of autologous stem cell
transp...
Timeline of cancer
Timeline of cancer
Upcoming SlideShare
Loading in...5
×

Timeline of cancer

2,182

Published on

Published in: Health & Medicine, Technology
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
2,182
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
30
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Timeline of cancer

  1. 1. TIMELINE OF CANCER Prepared By Mr. Naveen Kadian
  2. 2. 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.”
  3. 3. 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.
  4. 4. 3000 B.C. 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.
  5. 5. 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.
  6. 6.  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 long history.
  7. 7. 400 B.C.  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 bile.  He believed that it was best to leave cancer alone because those who got treatment didn't survive as long.  Hippocrates is credited with being the first to recognize the difference between benign and malignant tumors.
  8. 8. 168 B.C. 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.
  9. 9. 657 A.D. 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 cauterization.
  10. 10. 1190 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 dangerous."
  11. 11. 1713 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 Workers).
  12. 12. 1727  In 1727, however, Le Clerc suggested cutting out swellings, polyps, and tumefactions before they became cancerous.
  13. 13. 1761 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”.
  14. 14. 1775 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.
  15. 15. 1779 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.
  16. 16. 1829  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.
  17. 17. 1838  Johannes 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 came from 'blastema' (the undifferentiated tissue from which it was believed that cells arose from) between normal tissues.
  18. 18. 1846 Advent of general anesthesia opens the door for modern cancer surgery In October 1846, a Boston dentist named William T.G. Morton provides the first public 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, ultimately eliminating the excruciating pain experienced by surgical patients until that time, and making the modern era of surgery possible.
  19. 19. 1863-1867 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 liquid.
  20. 20. 1878  Theodore 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 carcinoma.
  21. 21. 1880s 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.
  22. 22. 1889 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.
  23. 23. 1893 Bacterial toxins linked to cancer treatment, presaging BCG in Bladder cancer prevention.
  24. 24. 1896  In 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 contribution.  In 1896, Beatson presaged moleculartargeted hormonal prevention of breast cancer by observing that oophorectomy had a beneficial effect on advanced breast cancer.  Removal of the ovaries is performed for the first time to treat breast cancer.
  25. 25. 1898  Marie and Pierre Curie discover radium and later use it to treat tumors.
  26. 26. 1899  Tage Anton Ultimus Sjogren was the first to successfully treat cancer with X-rays.
  27. 27. 1900 Thor Stenbeck cures a patient with skin cancer using small doses of daily radiation therapy. This technique is later referred to as fractionated radiation therapy.
  28. 28. 1903  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.
  29. 29. 1907  Discovery of human papillomavirus (HPV)
  30. 30. 1910 A major breakthrough in model 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 injected hens.
  31. 31. 1914 Theodor Boveri proposed the Somatic Mutation Theory of Cancer. He believed that cancer was caused by abnormal chromosomes.
  32. 32. 1915  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
  33. 33. 1925  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 been begun.
  34. 34. 1926 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.
  35. 35. 1928  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.
  36. 36. 1932  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 cancer
  37. 37. 1933  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 Singer
  38. 38. 1935  The first published report of BCG as a cancer vaccine (in Swedish patients) came out in 1935.
  39. 39. 1937  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 methotrexate.
  40. 40. 1939  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.
  41. 41. 1941  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 work. “Clinical COX-2 targeting in familial adenomatous polyposis (FAP) and sporadic colorectal adenoma patients was based in part on two important laboratory advances”.
  42. 42. 1942  Louis Goodman and Alferd Gilman use nitrogen musturd to treat patient with non-Hodgkin’s lymphoma and demonstrate for the first time that chemotherapy can induce tumor regression.
  43. 43. 1943  Introduction of Pap test leads to dramatic declines in cervical cancer deaths 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 is limited.  The first electron linear accelerator is designed for radiation therapy. Today, it is widely used for treatment of cancer.
  44. 44. 1945  Felix Bloch and Edward Purcell discover nuclear magnetic resonance used today to detect brain tumors and other cancers.
  45. 45. 1946  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
  46. 46. 1947 First-ever remission of pediatric leukemia 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.
  47. 47. 1948  Syndey Farber uses Antifolates to succesfully induce remission in children with acute lymphoblastic leukemia (ALL).  George Hitchings and Gertude Elion isolated a substance that inhibited adenine metabolism.
  48. 48. 1949 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.
  49. 49. 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.
  50. 50. 1951  George Hitchings and Gertude Elion they had developed two drugs that would later play an important role in the treatment of acute leukemia: 6-thioguanine 6-mercaptopurine
  51. 51. 1952  Development of mechlorethamine (Mustargen) and chlorambucil.
  52. 52. 1953  Slaughter and colleagues helped clarify carcinogenesis in the oral cavity and other epithelial sites with their report of the concept “ field cancerization”
  53. 53. 1954  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.
  54. 54. Mid 1950s  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 colorectal cancer.
  55. 55. 1956  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.
  56. 56. 1957  Approval of Fluorouracil.
  57. 57. 1958  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 chemotherapy.  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.
  58. 58. 1959  The Food and Drug Administration (FDA) approved the alkylating agent Cyclophosphamide.
  59. 59. 1960 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 of cancer. 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 Hodgkin's disease.
  60. 60. 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 other cancers.
  61. 61.  Lars Leksell develops the Gamma Knife a radiosurgical tool that uses a high dose of radiation to eradicate cancerous cells.
  62. 62. 1962  Malcolm Bagshaw develops a type of radiation therapy called high-dose, small-field radiation to treat prostate cancer without the need for surgery.
  63. 63. 1963  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 colleagues.
  64. 64. 1964  The Epstein-Barr virus is linked to human cancer for the first time.
  65. 65. 1965 • 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 standard treatment. • 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 treatment today.
  66. 66. 1966  Discovery of Estrogen receptor by Elwood V. Jensen  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 Research
  67. 67. 1967  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).
  68. 68. 1967  Arthur Kornberg synthesizes biologically active DNA in a test tube, spurring development of engineering techniques in medicine and biotechnology.
  69. 69. 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 of cancer. 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 with surgery.
  70. 70. Early 1970 Increased use of radioactive “seeds” to target prostate and other cancers 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 relatively unaffected. 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.
  71. 71. 1970’s 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.
  72. 72. 1970 Leonard Herzenberg develops the flourescenceactivated cell sorter, revolutionizing the study of cancer cells. Vinvcet Devita and colleagues cure lymphomas with combination chemotherapy.
  73. 73. 1971 More limited mastectomy proven effective for early-stage breast cancer 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.
  74. 74. 1972  Emil Frei and colleagues demonstrate that chemotherapy given after surgical removal of osteosarcoma can improve cure rates. (Adjuvant Chemotherapy)
  75. 75. 1974  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.
  76. 76. 1974  Dr. Lawrence Einhorn finds a cure for advanced testicular cancer. This changes the cure rate from 5 percent to 60 percent.
  77. 77. 1975 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 cancer 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.
  78. 78. 1975  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.
  79. 79. 1976  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 Peyton Rous  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.
  80. 80. 1977 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.
  81. 81. 1978  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.
  82. 82. Late 1970s 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.
  83. 83. 1981 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%.
  84. 84. 1982 Limited surgery helps rectal cancer patients avoid colostomies 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.
  85. 85. 1983  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.
  86. 86. 1984  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 cancers.  Jeffery Sklar, Michael Cleary (pictured), and fellow Stanford scientists use purified genetic probes to diagnose cancer.
  87. 87. 1986 • 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.
  88. 88. 1986 • Tamoxifen reduces breast cancer recurrence Tamoxifen (Novaldex) is approved as adjuvant therapy for post-menopausal women following breast cancer surgery.
  89. 89. 1988  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.
  90. 90. 1989 • 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, reduce infections 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 hospitalizations.
  91. 91. 1985-1991 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.
  92. 92. Late 1980s 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.
  93. 93. Early 1990s Laparoscopic surgery minimizes pain, recovery time for several cancers 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 effectiveness.
  94. 94. Early 1990s 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 tissue.
  95. 95. 1990  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.
  96. 96. 1991  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 gastric neoplasia.  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.
  97. 97. 1991  The U.S. Human Genome project begins. The first gene transfers in humans also take place in that same year
  98. 98. 1992 • 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 patients. • FDA approved Paclitaxel (Taxol) which becomes the first ‘blockbuster’ oncology drug.
  99. 99. 1992  Sentinel lymph node biopsy determines cancer’s spread with fewer side effects 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.
  100. 100. 1993  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.
  101. 101. 1994  DuBois (AACR president in 2008 – 2009) and colleagues showed in 1994 that COX-2 is up-regulated in human colorectal adenomas and adenocarcinomas.  In 1994, investigators reported the first systematic study of methylation as a very early event of human colorectal neoplasia.
  102. 102. 1995  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 plans.  Investigators showed that targeting to reverse methylation can prevent intestinal neoplasia in mice.
  103. 103. 1996  Taketo and colleagues showed COX-2 targeting was effective against intestinal neoplasia in adenomatous polyposis coli (Apc) knockout mice.
  104. 104. 1997  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.
  105. 105. 1997 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 essentially cured. 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 above 50%.
  106. 106. 1998  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 genes.  In 1998, the FDA approved Valrubicin for preventing BCG-refractory superficial bladder tumor recurrence.
  107. 107. 1998  Chemotherapy before surgery helps more women benefit from breast-conserving treatment 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.
  108. 108. 1999  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.
  109. 109. Late 1990s 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 %.
  110. 110. Late 1990s 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.
  111. 111. 2000  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.
  112. 112. 2001  Studies by Brain Druker lead to FDA approval of Imatinib mesylate (Glivec) for chronic myelogenous leukemia, a new paradigm for targeted therapy in oncology.
  113. 113. 2003  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 IFOX regimen.  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 the disease.
  114. 114. 2003  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 spread.  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 insignificant disease.
  115. 115. 2004 • 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 targeted agents.
  116. 116. 2004  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.
  117. 117. 2006  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.
  118. 118. 2006  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.
  119. 119. 2007  The FDA approves Nexavar, an oral inhibitor for liver cancer. This is the only drug approved for liver cancer.
  120. 120. 2008  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 early 1980s.
  121. 121. 2009  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 prevention.
  122. 122. 2010  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, however, continues.
  123. 123. 2010 First drug shown to improve survival for patients with advanced melanoma 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.
  124. 124. 2010  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.
  125. 125. 2011  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 myeloma.
  126. 126. 2011  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.
  127. 127. 2011  New biomarkers to predict response to therapy in lung cancer patients 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.
  128. 128. 2011  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.
  129. 129. 2011  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.
  130. 130. 2011  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.
  131. 131. 2011  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.
  132. 132. 2011  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.
  133. 133. 2011  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.
  134. 134. 2011  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.
  135. 135. 2011  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 regimen.  FDA Approval of Everolimus (Afinitor) for the treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease.  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.
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×