*Some of the information in this history was adapted from a project entitled “Landmarks in Cancer Research”, which was developed in honor of the Centennial of the American Association for Cancer Research.*

Cancer: (Latin word, crab) Any malignant growth or tumour from an abnormal and uncontrolled division of body cells. (Reference: Canadian Oxford Dictionary 2004)

460-377 BC.

Hippocrates recognized the differences between malignant (cancer) and benign (normal) cells. The appearance of certain cancers of the skin (melanoma) reminded him of the shape of a crab (karkinos).

Cancer was also described in old civilizations of Asia, South America and Egypt. Cancer of the bones (osteosarcoma) was diagnosed in Egyptian mummies.

Around 1775

In England, several young boys worked as chimney sweepers. Sir Percival Pott (MD) noted that several of these boys died from cancer of the scrotum.

1907

First epidemiologic study binding sun exposure and skin cancer.

1910

The first cultures of cancer cells are made in laboratory (in vitro). This makes it possible to test future drugs.

1914

Researchers postulate that cancer could be caused by mutations.

1916

Demonstration that hormones are implicated in tumour development (oophorectomy - or the ablation of the ovaries - reduces the rate of breast cancer in mice).

1928

Genetic mutations are proposed to be at the origin of cancer. (They are thus not only caused by viruses!).

Dr. Papanicolaou reports the presence of cancer cells in cervical smears. It will take 32 years (until 1960) before the “PAP” test is accepted to detect cancers.

By using the drosophila (fruit fly), researchers demonstrate in 1928 that X-rays are mutagenic.

1930

Researchers isolate and identify the first carcinogenic product: benzopyrene, the active ingredient in tar.

1932

The injection of synthetic hormones induced breast cancer in mice, confirming the 1916 demonstration.

1937 

It is shown that the transplant of only one cell is sufficient to transmit leukemia in animals. This represents the first demonstration of the existence of cancer stem cells.

1938

Researchers discover that cancer induced by chemicals is the result of two different stages: initiation and promotion. Various chemicals are responsible for these two events.

1939

Angiogenesis is discovered, the process by which cancer cells allow the growth of new blood vessels. This will become a therapeutic avenue.

1940

Experiments in animals show that a reduction in calories in a diet reduces tumour development. It is not until 2000 when obesity affects more and more people that the importance of this discovery is realized.

1944

By studying bacteria, Avery and collaborators identify DNA as the genetic material of a cell.

1945

The Cancer Research Society is founded in 1945 by a group of 4 women dedicated to finding a cure to cancer.

1946

The first chemotherapy takes place: following observations reporting that soldiers exposed to nitrogen mustard have reduced amounts of white blood cells. Studies show that derivatives of this compound slow down the growth of leukemic cells, and derivatives of nitrogen mustard are the first alkylating agents, a family of treatments still used today in the treatment of certain cancers.

1950

A synthetic DNA analog is used against cancer cells.  Such compounds, such as the 5-fluorouracil in particular, are still used today.

1950

Studies bind nicotine to lung cancer.

1951

Dr Harold Johns develops the “cobalt bomb” (unit of cobalt 60) for radiotherapy. This type of irradiation is still used today.

It is also in 1951 that the use of ultrasounds begins in order to detect cancer cells.

1956

The first chemotherapy to counter solid tumours (choriocarcinoma) is successful. This therapy used another folate antagonist called the methotrexate which is still in use today.

1960

The first growth factor (NGF: nerve growth factor) is identified. Growth factors represent therapeutic targets today (EGF in breast cancer, a receptor identified in 1967).

1963

Chemotherapy cures Burkitt lymphoma, a cancer caused by a virus
(the Epstein-Barr virus).

1966

The effectiveness of combining various drugs against cancer is shown. The use of MOPP (a combination of 4 products: nitrogen mustard, vincristine, prednisone and procarbazine) makes it possible to cure Hodgkin lymphoma.

1966 also sees the invention of the first apparatus specifically made for mammography.

1971 - An important year:

Researchers show that a natural product, taxol, inhibits the growth of leukemic cells.  Chemical synthesis of this product allows for its use against ovarian cancer.

After studying cancer transmission (in retinoblastoma) in children, Knudson proposes that cancer requires at least two changes. His assumptions proved to be exact in the majority of human cancers.

In 1971, researchers show that tumour cells secrete factors which promote new blood vessels (a phenomenon called angiogenesis). The subsequent identification of such factors will make them molecular targets.

1972

The spinal cord transplant is used for the first time in leukemia treatment. In this procedure, the transplanted cells replace those which were destroyed by radiotherapy.

1974

DNA replication errors are identified as causes of tumours.

Cytogenetic makes it possible to identify chromosomal rearrangements specific to certain types of leukemia and lymphomas. This will later lead to therapy development of a targeted drug (Imatinib or Gleevec) against proteins coming from such rearrangements (protein BCR-ABL).

1976

The combination of radiotherapy and chemotherapy makes it possible to prolong the remission of 80% of children with acute lymphocytic leukemia (ALC).

1977

Following the remarkable successes obtained in animal models, Tamoxifen is approved for the treatment of breast cancer.

MRI (magnetic resonance imaging) scans are invented, allowing the detection of tumours at an early stage.

1978

Animal studies show that tobacco nitrosamines cause cancer; these substances are linked to mouth and lung cancer development.

1979

The p53 gene is discovered. It will later be shown that p53 mutations are implicated in nearly 50 % of human tumours.

Tyrosine kinases are discovered. Kinases are a type of enzymes that modify proteins. These kinases will later on become therapeutic targets.

1980

High blood levels of prostate specific antigens (PSA) are associated with prostate cancer. This association leads to the development of the first routine marker assay in the tracking of cancer.

Studies show that cancer cells secrete enzymes enabling them to degrade their surrounding medium, thus giving them access to other blood vessels and tissues, a phenomenon called metastasis.

1982

It is shown that viral infections by Helicobacter pylori cause ulcers of the stomach, which under certain conditions can lead to cancer.

1983

The human papillomavirus (HPV) is identified as the cause of cervical cancer.  This discovery will lead to the development of a vaccine to prevent this type of cancer.

Using a molecular model, it is also demonstrated that several steps are mandatory in the development of cancer.

1986

Telomerase and the retinoblastoma (Rb) tumour suppressor gene are identified.

1987

It isdemonstrated that the growth factor receptor gene Her-2/neu is amplified in 15 % of stage 1 breast cancers.  The HER-2/neu marker will later become the therapeutic target of transtuzumab (Herceptin), which will increase the survival rate of Her-2/neu positive breast cancer patients.

1990

Mutations of the BRCA1 gene are associated with hereditary transmission of breast cancer.

1991

Gene p53 changes in liver cancer cells are associated with aflatoxine, an environmental carcinogen. Aflatoxine can develop in several foods which are exposed to certain Aspergillus mushrooms, such as corn and nuts.

1993

Michael Smith from Canada receives the Nobel Prize in chemistry for his work on directed mutagenesis, which makes it possible to introduce mutations into genes at precise locations.

1995

DNA microarray technology is developed, making it possible to analyze the expression and the presence of mutations in thousands of genes simultaneously. This technology will allow the development of personalized therapies based on the particular modifications present in the tumours of patients.

1998

The addition of monoclonal antibodies (transtuzumab, Herceptin) to chemotherapy significantly improves the survival of patients with advanced breast cancer.

2001

Imatinib (Gleevec) represents the first targeted molecular therapy used against chronic myelogenous leukemia; it allows for a remission among these patients.

The sequence of the human genome is obtained. The genome of various tumours will now be the focus of future work in order to identify the mutations leading to cancer development.

2003

Bortezomib (Velcade), a new type of drug targeting the cellular protein degradation system, is used and is effective among patients with multiple myeloma.

2004

A vaccine against the human papilloma virus (HPV) is used to prevent cervical cancer.

Bevacizumab (Avastin), an antibody directed at the essential protein in angiogenesis, is used in combination with chemotherapy to increase the survival rate of metastatic colon cancer patients.

2008

The Nobel Prize in Medicine is given to Harald zur Hausen from Germany for his work on HPV and cervical cancer.

2009

The Nobel Prize in Medicine 2009 was awarded jointly to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase".
 

References