Institute of Cancer Research
Encyclopedia
The Institute of Cancer Research (the ICR) is a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 research institute
Research institute
A research institute is an establishment endowed for doing research. Research institutes may specialize in basic research or may be oriented to applied research...

 located in London
London
London is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...

, United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

 and a constituent college of the federal University of London
University of London
-20th century:Shortly after 6 Burlington Gardens was vacated, the University went through a period of rapid expansion. Bedford College, Royal Holloway and the London School of Economics all joined in 1900, Regent's Park College, which had affiliated in 1841 became an official divinity school of the...

. The ICR was founded in 1909 as a research department of the Royal Marsden Hospital and joined the University of London in 2003. It has been responsible for a number of breakthrough discoveries, including that the basic cause of cancer is damage to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

.

Together with the Royal Marsden Hospital the ICR forms the largest comprehensive cancer centre in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, and was ranked first amongst all British higher education institutions in the Times Higher Education 2008 Research Assessment Exercise Table of Excellence. In addition to its research activities the ICR provides both taught postgraduate degree programmes and research degrees and currently has around 340 students. The ICR occupies two sites, one in Chelsea
Chelsea, London
Chelsea is an area of West London, England, bounded to the south by the River Thames, where its frontage runs from Chelsea Bridge along the Chelsea Embankment, Cheyne Walk, Lots Road and Chelsea Harbour. Its eastern boundary was once defined by the River Westbourne, which is now in a pipe above...

 in Central London
Central London
Central London is the innermost part of London, England. There is no official or commonly accepted definition of its area, but its characteristics are understood to include a high density built environment, high land values, an elevated daytime population and a concentration of regionally,...

 and one in Sutton
Sutton, London
Sutton is a large suburban town in southwest London, England, and the administrative headquarters of the London Borough of Sutton. It is located south-southwest of Charing Cross and is one of the major metropolitan centres identified in the London Plan. The town was connected to central London by...

 in southwest London. It had a total income of £83.9 million in 2009/10, of which £49.8 million was from research grants and contracts.

The ICR receives its external grant funding from the government body the Higher Education Funding Council for England
Higher Education Funding Council for England
The Higher Education Funding Council for England is a non-departmental public body of the Department for Business, Innovation and Skills in the United Kingdom, which has been responsible for the distribution of funding to Universities and Colleges of Higher and Further Education in England since...

, from government research council bodies and from charities including the Wellcome Trust
Wellcome Trust
The Wellcome Trust was established in 1936 as an independent charity funding research to improve human and animal health. With an endowment of around £13.9 billion, it is the United Kingdom's largest non-governmental source of funds for biomedical research...

, Cancer Research UK
Cancer Research UK
Cancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...

, Breakthrough Breast Cancer
Breakthrough Breast Cancer
Breakthrough Breast Cancer is a United Kingdom charity committed to fighting breast cancer through research, campaigning and education. Its vision is "to work for a future free from the fear of breast cancer".-History:...

 and Leukaemia & Lymphoma Research. It also receives voluntary income from legacies and from public and corporate donations. It runs the Everyman Campaign
Everyman Campaign
The Everyman Campaign is a campaign that was launched in the UK by The Institute of Cancer Research in 1997. It seeks to raise awareness of testicular and prostate cancer and to raise funds to research treatments....

 fundraising appeal, which raises awareness of male cancers and funds research into testicular and prostate cancer at the Everyman Centre, which is based at the ICR.

20th century

The ICR was founded in 1909, when a new laboratory building adjoining The Cancer Hospital (later named the Royal Marsden Hospital) was established with Dr Alexander Paine as its first Director. In 1910 Dr Robert Knox was appointed to head the Electrical and Radio-therapeutic Department at The Cancer Hospital and established the first professionally designed X-ray Department
Radiology
Radiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...

 for treatment and diagnosis in Britain. The Cancer Hospital Research Institute was officially opened by Prince Arthur, the Duke of Connaught
Prince Arthur, Duke of Connaught and Strathearn
Prince Arthur, Duke of Connaught and Strathearn was a member of the shared British and Saxe-Coburg and Gotha royal family who served as the Governor General of Canada, the 10th since Canadian Confederation.Born the seventh child and third son of Queen Victoria and Prince Albert of Saxe-Coburg and...

 in 1911. In 1921 Professor Archibald Leitch was appointed Director of The Cancer Hospital Research Institute. The Institute became a postgraduate School of the University of London
University of London
-20th century:Shortly after 6 Burlington Gardens was vacated, the University went through a period of rapid expansion. Bedford College, Royal Holloway and the London School of Economics all joined in 1900, Regent's Park College, which had affiliated in 1841 became an official divinity school of the...

 in 1927. In 1931 Professor Sir Ernest Kennaway FRS
Ernest Kennaway
Sir Ernest Laurence Kennaway was a British pathologist and Royal Medal winner. He first became interested in natural life when, due to a childhood illness, he was encouraged to spend time outdoors. He was trained at University College London, and in 1898 was accepted into New College, Oxford on an...

 became Director of the Institute. In 1932 a research team led by Professor Kennaway fractionated coal tar and isolated benzo[a]pyrene, which he identified as one of the chemical constituents that induced cancer in mice. These were the first research findings to show that a pure chemical substance can cause cancer. In 1936 Professor Kennaway proposed the potential of a link between smoking
Smoking
Smoking is a practice in which a substance, most commonly tobacco or cannabis, is burned and the smoke is tasted or inhaled. This is primarily practised as a route of administration for recreational drug use, as combustion releases the active substances in drugs such as nicotine and makes them...

 and lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

. The Cancer Hospital Research Institute moved to a new site on Fulham Road
Fulham Road
Fulham Road is a street in London, England, that runs from the A219 road in right in the centre of Fulham, in the London Borough of Hammersmith and Fulham, through Chelsea to Brompton Road Knightsbridge and the A4 in Brompton, in the Royal Borough of Kensington and Chelsea.Fulham Road runs parallel...

 in Chelsea in 1939 and was renamed the Chester Beatty Research Institute. In 1946 Professor Sir Alexander Haddow FRS became the Director of the Chester Beatty Research Institute. In 1947, while conducting research at the Institute, Professor David Galton became the first physician in the world to use aminopterin
Aminopterin
Aminopterin , a 4-amino analog of folic acid, is an antineoplastic drug with immunosuppressive properties used in chemotherapy. Aminopterin is a synthetic derivative of pterin. Aminopterin works as an enzyme inhibitor by competing for the folate binding site of the enzyme dihydrofolate reductase...

 (the forerunner of the methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...

 drug) in the treatment of adult leukaemia, producing remission in some cancer patients.

During the 1940s Haddow established a Clinical Chemotherapy Research Unit - the first such unit in Europe - in partnership with the Royal Marsden Hospital and under Galton's leadership. The partnership was unique at the time in being able to take the drug discoveries directly into a partner hospital for clinical trials in cancer patients. The unit led to the Institute's discovery of three successful chemotherapy drugs in the 1950s: busulphan (Myleran), chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...

 (Leukeran) and melphalan
Melphalan
Melphalan hydrochloride is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents.An alkylating agent adds an alkyl group to DNA...

 (Alkeran).

In 1954 the Institute was officially renamed The Institute of Cancer Research (ICR). The ICR established a second campus in Sutton, Surrey in 1956. Whilst working at the ICR in 1961, Professor Jacques Miller
Jacques Miller
Jacques Francis Albert Pierre Miller AC FRS is a distinguished research scientist. He is famous for having discovered the function of the thymus and for the identification, in mammalian species of the two major subsets of lymphocytes and their function.-Early life:Miller was born on 2 April 1931,...

 discovered the immunological role of the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

, as the repository of a special class of lymphocytes (T cells) essential for the mounting of an immune response.

In 1952 the ICR's Dr Eric Boyland had proposed that certain chemicals that cause cancer (carcinogens) react with DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 through an alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

 mechanism that damaged the DNA molecule. In follow-up research at the ICR in 1964, Professors Peter Brookes and Philip Lawley proved that chemical carcinogens act by damaging DNA, leading to mutations and the formation of tumours, proving that cancer is a genetic disease based on mutational events.

Scientists at the ICR were instrumental in the development of one of the world's most widely used anti-cancer drugs, carboplatin
Carboplatin
Carboplatin, or cis-Diammineplatinum is a chemotherapy drug used against some forms of cancer...

 (Paraplatin).
Carboplatin’s development began in 1970 after US scientists discovered the platinum-based compound cisplatin was effective against many tumours – but had serious side-effects. A team of ICR and RMH scientists and clinicians including Professors Ken Harrap and Tom Connors, Dr Hilary Calvert and Hospital Consultant Dr Eve Wiltshaw recognised its potential but also the need for a less toxic alternative. In collaboration with the pharmaceutical company Johnson Matthey plc the ICR scientists evaluated some 300 different platinum-containing molecules and developed a series of second generation compounds, of which carboplatin was selected as the lead. The first clinical trial of carboplatin was carried out in 1981 and it launched commercially as Parplatin (manufacturered by Bristol-Myers) in 1986 .

Carboplatin is in use for a range of cancers including ovarian and lung. For the development of these platinum-based anticancer drugs the ICR, together with The Royal Marsden Hospital and Johnson Matthey plc
Johnson Matthey
Johnson Matthey plc is multinational chemicals and precious metals company headquartered in London, United Kingdom.It is listed on the London Stock Exchange and is a constituent of the FTSE 100 Index.-History:...

, received the Queen’s Award for Technological Achievement
Queen's Awards for Enterprise
The Queen's Awards for Enterprise is an awards programme for British businesses and other organizations who excel at international trade, innovation or sustainable development. They are the highest official UK awards for British businesses...

 in 1991.

During the 1980s ICR scientists including Professors Hilary Calvert, and Ken Harrap and Dr Ann Jackman developed raltitrexed
Raltitrexed
Raltitrexed is an antimetabolite drug used in cancer chemotherapy. It is an inhibitor of thymidylate synthase, and is manufactured by AstraZeneca.-Mechanism of action:...

 (Tomudex) at the ICR, a drug active for the treatment of colon and other cancers. In 1983 research teams at the Chester Beatty Laboratory of the ICR led by Professors Chris Marshall FRS and Alan Hall FRS discovered N-RAS
Neuroblastoma RAS viral oncogene homolog
NRAS is an enzyme that in humans is encoded by the NRAS gene. It was discovered by researchers at the Institute of Cancer Research, funded by the Imperial Cancer Research Fund , and named NRAS, for its initial identification in human neuroblastoma cells.-External links:*...

, one of the first human cancer transforming genes (oncogenes). Professor Alan Hall went on in 1992 to discover that the molecular mechanism for the motility behaviour of animal cells (cell to cell attachment and cell movement) is through control of cytoskeletal assembly by specific GTPase-proteins, known as Rho
Rho family of GTPases
The Rho family of GTPases is a family of small signaling G protein , and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants...

 and Rac
Rac (GTPase)
Rac is a subfamily of the Rho family of GTPases, small signaling G proteins .The subgroup include:*Rac1*Rac2*Rac3*RhoG...

. The discovery is of fundamental significance in cancer research since cell motility is a key feature of cancer cell behaviour during metastasis (the spread of tumours around the human body).

In 1994 an ICR team led by Professor Michael Stratton discovered the gene BRCA2, which has been linked to breast cancer, prostate cancer and ovarian cancer. Professor Ashworth’s team in the Breakthrough Breast Cancer Research Centre at the ICR established the connection between mutations in the BRCA2 gene and the operation of DNA repair pathways in cancer cells. This later led to the development of a PARP inhibitor
PARP inhibitor
PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase . They are developed for multiple indications; the most important is the treatment of cancer...

 drug, olaparib
Olaparib
Olaparib is a chemotherapeutic agent developed by KuDOS Pharmaceuticals and later by Astra Zeneca. It is an inhibitor of PARP, an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which includes many ovarian, breast and prostate cancers...

, which targets the DNA repair pathways of cancer cells. A Phase I trial of olaparib found in June 2009 that tumours shrank or stabilised for more than half of patients with BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...

 and BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....

 mutations It is believed that the drug may also be useful in other patients whose cancer it is linked to an error in their DNA repair pathway.

In 1999 the Chester Beatty Laboratory in Chelsea was redeveloped and extended to incorporate the Breakthrough Toby Robins Breast Cancer Research Centre, which was opened by HRH The Prince of Wales
Charles, Prince of Wales
Prince Charles, Prince of Wales is the heir apparent and eldest son of Queen Elizabeth II and Prince Philip, Duke of Edinburgh. Since 1958 his major title has been His Royal Highness The Prince of Wales. In Scotland he is additionally known as The Duke of Rothesay...

 in 1999.

21st century

In 2000 Professor Michael Stratton at the ICR initiated the Cancer Genome Project
Cancer Genome Project
The Cancer Genome Project, based at the Wellcome Trust Sanger Institute, aims to identify sequence variants/mutations critical in the development of human cancers...

, which was aimed at capitalizing on the knowledge from the Human Genome sequence to screen all human genes in cancer cells to identify those genes responsible for specific cancers. The project was established at the genome sequencing facilities of the Wellcome Trust Sanger Institute near Cambridge, of which Professor Stratton is now the Director. One of the first major achievements of the Cancer Genome Project has been the characterisation of the cancer gene BRAF in collaboration with ICR scientists Professors Chris Marshall and Richard Marais. The research by the ICR team, published in June 2002, revealed that damage to the BRAF gene could cause up to 70 per cent of melanoma skin cancers. This has been instrumental in speeding up the development of new drugs for the treatment of malignant melanoma. Since 2002 the ICR has been working to develop drugs that inhibit BRAF in melanoma and other cancers where the gene is defective.

In the five years from 2004/05, the ICR developed on average two drug development candidates per year. Since 2006, it has licenced three novel series of anti-cancer drugs to major pharmaceutical companies: Hsp90
Hsp90
Hsp90 is a molecular chaperone and is one of the most abundant proteins expressed in cells. It is a member of the heat shock protein family, which is upregulated in response to stress...

 inhibitors to Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...

, PKB
AKT
Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...

 inhibitors to AstraZeneca
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...

 and PI3Kinase
Phosphoinositide 3-kinase
Phosphatidylinositol 3-kinases are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In response to lipopolysaccharide, PI3K phosphorylates p65, inducing...

 inhibitors to Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...

. The PIl3Kinase inhibitor GDC-0941, licensed to Genentech by Piramed, is thought to have potential in a range of human cancers. In laboratory experiments, ICR scientists found that the drug reduced the growth of glioblastoma (the most common form of brain tumour), it decreased the growth of ovarian tumours and in other studies, it was active against cell lines derived from other human cancers.

In March 2009, a key enzyme involved in cancer spread, metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

, a process that causes 90% of all cancer patient deaths, was found for breast cancer and later confirmed to be involved in the spread of bowel cancer. Also in 2009, the Integrative Network Biology initiative (INBI) was established with the aim of performing quantitative systems and network biology studies of the metastatic process. As part of this initiative, the ICR also established core facilities in proteomics equipped with state-of-the-art mass spectrometers and in supercomputing to support research projects demanding computational systems biology.

In conjunction with The Royal Marsden NHS Foundation Trust
The Royal Marsden NHS Foundation Trust
The Royal Marsden Hospital is a specialist cancer treatment hospital in London, England. It is an NHS Foundation Trust, and operates facilities on two sites:*The Chelsea site in Brompton, next to the Royal Brompton Hospital, on Fulham Road...

, the ICR tested a promising new prostate cancer drug called abiraterone
Abiraterone
Abiraterone is a drug used in castration-resistant prostate cancer . It is formulated as the prodrug abiraterone acetate and sold under the trade name Zytiga...

, which it discovered and developed. A randomised placebo-controlled Phase III trial reported in October 2010 that abiraterone could extend survival in some men with late stage prostate cancer. The trial, funded by Janssen Pharmaceutical Companies
Janssen Pharmaceutica
Janssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...

, included 1,195 patients from 13 countries whose advanced prostate cancer had stopped responding to standard therapies. Abiraterone extended the average overall survival of patients from 10.9 months to 14.8 months compared to a placebo, without many of the unpleasant side-effects associated with conventional chemotherapy. The FDA in April 2011 approved the drug for sale in the US under the trade name Zytiga .

Research

The ICR pursues its research focused into three main research themes: genetic epidemiology
Genetic epidemiology
Genetic epidemiology is the study of the role of genetic factors in determining health and disease in families and in populations, and the interplay of such genetic factors with environmental factors...

, molecular pathology
Molecular pathology
Molecular pathology is an emerging discipline within pathology which is focused in the study and diagnosis of disease through the examination of molecules within organs, tissues or bodily fluids....

, and therapeutic development. These areas of research are essential for the development of personalised cancer medicine.

Towards this aim, the ICR and The Royal Marsden are currently building a dedicated £17 million Centre for Molecular Pathology (CMP), which is planned for completion in 2012. The centre will exploit the increasing availability of information about the genetic make-up of different cancer types, in order to design new "personalised" treatments that target cancers' specific molecular defects. The CMP also aims to develop molecular diagnostic techniques that will accurately predict who will benefit most from a treatment, ensuring a patient receives the optimum drug(s) for the best possible outcome. The CMP will build on the organisations' existing expertise in breast, prostate and paediatric cancers, while providing opportunities for new developments in other cancers such as gastrointestinal, renal, gynaecological, melanoma, head & neck cancers and sarcomas.

The organisation’s research direction is set out in the ICR Scientific Strategy 2010 - 2015, which aims to develop key research areas while enhancing partnership affiliations. Its four objectives are to maintain, develop and exploit the unique relationship with the Marsden; to ensure a balanced portfolio of basic and applied research; to develop treatment regimes to the genetic makeup of patient and tumour (personalised medicine) and to recruit, retain and motivate the best staff.

External links

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