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Understanding the Causes and Mechanisms of Cancer






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Past Highlights
Improving Early Detection and Diagnosis

For nearly all cancers, treatment options and survival are related to the stage of disease at diagnosis. The prognosis is generally better and treatment usually more successful if the disease is detected and diagnosed early while still localized. Unfortunately, many cancers have no symptoms at early stages and are not detected until the disease is advanced. Methods to detect and diagnose cancer include imaging procedures and laboratory tests. Laboratory tests may identify cancer cells (e.g., urine cytology for bladder cancer), specific biomarkers (e.g., the KIT receptor protein for gastrointestinal stromal tumors), or, more recently, distinctive gene-expression microarray patterns (e.g., the Lymphochip for diagnosing different types of lymphoma; see The Leukemia and Lymphoma Molecular Profiling Project).

NCI actively invests in biomarker development programs and in research toward the development of advanced technologies for cancer detection and diagnosis. Some of these efforts are conducted in international laboratories and medical institutions.

One NCI-supported effort in this area is the Early Detection Research Network (EDRN) to identify early cancer biomarkers (described below). Other NCI-supported efforts that involve international collaborators and seek to improve methods for the early detection and diagnosis of cancer are described here.

DNA microarray technology is a powerful new research tool that allows scientists to assess the level of expression of a large subset of the 100,000 human genes in a cell or tissue. This technology can quickly produce a snapshot of the genes that are active in a tumor cell, critical information in narrowing the precise molecular causes of a cancer.
DNA microarray technology is a powerful new research tool that allows scientists to assess the level of expression of a large subset of the 100,000 human genes in a cell or tissue. This technology can quickly produce a snapshot of the genes that are active in a tumor cell, critical information in narrowing the precise molecular causes of a cancer.

A collaboration of NCI and international researchers to construct tissue microarrays using human tissue specimens from Spain and Canada
NCI established the Program for the Assessment of Clinical Cancer Tests (PACCT) to ensure that promising cancer biomarkers are appropriately evaluated for clinical usefulness. A critical barrier to advancing cancer diagnostics is the lack of reference tissues for evaluating promising biomarkers. NCI identified two valuable collections of tissue specimens at the Institut Municipal d'Investigació Mèdica (IMIM) in Barcelona, Spain and the British Columbia Cancer Agency (BCCA) in Canada. The IMIM specimens are from bladder cancer patients diagnosed in five areas of Spain, and the BCCA specimens are from Canadian ovarian cancer patients. Although the BCCA microarrays are still under construction, the IMIM arrays are currently available. The IMIM microarrays are statistically designed to address major research questions in bladder cancer.

A collaboration with researchers at the University of Tokyo to develop a new optical imaging system to detect cancers at an early stage
The University of Tokyo is home to one of the world's premier fluorescence imaging laboratories, and NCI scientists are working with Japanese researchers to develop new activatable imaging probes for discovering cancers at an early stage. Activatable optical probes produce a signal and become detectable only after they reach their target. This new method can detect very small cancer nodules with very high sensitivity compared to current imaging methods, and it may also provide improved specificity over current methods.

A collaboration with Princess Margaret Hospital in Toronto, Canada to improve a magnetic resonance imaging-guided prostate biopsy system
Magnetic resonance imaging is emerging as the most effective diagnostic imaging tool for visualizing the anatomy and pathology of the prostate. NCI scientists are working with researchers at the Princess Margaret Hospital in Toronto to improve a magnetic resonance imaging-guided prostate biopsy system and to design the next generation of these devices. In addition, NCI is examining targeted biopsy specimens of prostate tissue to identify the next generation of molecular targets for diagnosis and therapy.

Images of Blood Leukocytes from an AIDS Patient Producing HIV
Images of Blood Leukocytes from an AIDS Patient Producing HIV

An international repository of HIV-infected human materials to serve as a resource for researchers around the globe
To encourage research on acquired immunodeficiency syndrome (AIDS) and cancer, NCI established the AIDS and Cancer Specimen Resource (ACSR). This international resource for tissue and biological samples serves researchers working in the fields of AIDS, cancer, virology, immunology, pathology, epidemiology, tumor biology, and assay development, as well as others. The ACSR is a repository of human immunodeficiency virus-1 (HIV-1)-infected materials from a wide spectrum of HIV-related or associated diseases and from appropriate HIV-negative controls. Special sets of specimens include serial samples from patients undergoing treatment in clinical trials. More than 100,000 individual specimens are contained in the repository, including samples from Africa, Brazil, Russia, and Thailand.

The Leukemia and Lymphoma Molecular Profiling Project (LLMPP), a collaboration of researchers in the United States, Canada, and Europe
NCI investigators are working with researchers at the University of Nebraska Medical Center in Omaha to define the gene expression profiles of all types of human lymphoid malignancies. The project is supported by an international collaboration involving investigators from the Southwest Oncology Group; the British Columbia Cancer Agency in Vancouver, Canada; the Norwegian Radium Hospital in Oslo, Norway; the University of Würzburg in Würzburg, Germany; the University of Barcelona in Barcelona, Spain; and St. Bartholomew's Hospital in London, England.

The LLMPP uses "Lymphochip" cDNA (complementary DNA) microarrays, which are enriched in genes that are expressed in and/or function in lymphocytes. Lymphochip microarrays allow measurement of the RNA expression levels of the represented genes. Gene expression profiles developed as a result of this project may someday be used for disease classification (diagnosis), prognosis, and therapy selection. Already, results from the LLMPP indicate that these profiles can improve diagnostic accuracy and provide prognostic information.

The LLMPP is initiating a multicenter clinical trial to evaluate a lymphoma diagnostic chip, called LymphDX, which was designed by the company Affymetrix in collaboration with NCI researchers using LLMPP data. The study will demonstrate the feasibility of disseminating the LymphDX microarray technology to all of the participating sites and will also evaluate the diagnostic utility of the LymphDX chip in a prospective study.

The American-Russian Cancer Alliance, a consortium of American and Russian institutes engaged in cancer research and education
The American-Russian Cancer Alliance (ARCA), established in 2001, is a consortium of American and Russian cancer research institutes that conducts scientific research and medical education conferences both in the United States and Russia. The participating institutes include the University of Maryland Greenebaum Cancer Center in Baltimore, Maryland; the Fox Chase Cancer Center in Philadelphia, Pennsylvania; and the Kurchatov Institute and the N.N. Blokhin Cancer Research Center in Moscow, Russia. The Fox Chase Cancer Center is an NCI-designated Comprehensive Cancer Center, while the Kurchatov Institute is Russia's premier nuclear research center. Among ARCA's programs is a groundbreaking effort funded by the United States to use Russia's expertise and nuclear facilities to produce radioisotopes for diagnostic and therapeutic applications in oncology.

In one project, scientists at the Fox Chase Cancer Center have been developing agents for positron emission tomography (PET) detection and staging of cancer using iodine-124 from the Kurchatov Institute. In another study, University of Maryland researchers are investigating novel ways to use isotopes to destroy blood vessels that feed malignant tumors. Their initial research focused on actinium-225, but now they are working with another isotope, polonium-210. In a third project, Fox Chase Cancer Center investigators are studying the use of bismuth-213 for the radiotherapy of solid tumors.

NCI provides support for the infrastructure of ARCA through a supplement to the Cancer Center Core Grant awarded to the Fox Chase Cancer Center. The Institute is also providing funding for a tobacco research grant involving Fox Chase and the N.N. Blokhin Cancer Research Center through the Fogarty International Center's International Tobacco and Health Research and Capacity Building Program. In March 2006, NCI supported a major conference in Moscow that was organized by three ARCA partners (the Fox Chase Cancer Center, the University of Maryland Greenebaum Cancer Center, and the N.N. Blokhin Cancer Research Center) and entitled "Prevention and Treatment of Tobacco-Related Cancers." Approximately 200 Russians attended this conference, including a representative of the Russian legislature, as well as the U.S. Ambassador to the Russian Federation. Several NCI scientists were invited speakers. In Autumn 2006, NCI will host a workshop, involving ARCA partners, in Bethesda, Maryland, on the use of isotopes in cancer diagnosis and treatment.

In conjunction with ARCA, NCI's Office of International Affairs (OIA) is sponsoring a 1-year (2006-2007) training visit of a Russian scientist from Lomonosov Moscow State University to the University of Maryland School of Medicine's Division of Nuclear Medicine. In 2005, OIA sponsored shorter training visits of three Russian scientists to the same institution. In February 2005, NCI sponsored a visit of three representatives from the N.N. Blokhin Cancer Research Center to various cancer research centers and governmental and non-governmental organizations in the United States, including NCI. The purpose of the visit was to observe "best practices" in cancer communications to be adapted in Russia. Also in 2005, NCI sponsored six Russians to participate in the Institute's Summer Curriculum in Cancer Prevention and Control which is described in NCI's Summer Course on the Principles and Practice of Cancer Prevention and Control.

An international conference cosponsored by NCI and the European Organization for Research and Treatment of Cancer (EORTC) to share data on cancer molecular markers
In 2004, the third EORTC-NCI International meeting to discuss cancer molecular markers drew more than 200 participants from Europe, Asia, Africa, and the United States. NCI staff members were involved in planning the meeting and participated as session chairs and speakers. During the meeting, staff from the NCI and the U.S. Food and Drug Administration and members of the EORTC developed and presented a 1-day tutorial for industry on pathways for development of clinical laboratory tests using cancer molecular markers. The next international EORTC-NCI meeting on cancer markers is scheduled to be held in September 2006.

NCI's Early Detection Research Network
In 2000, NCI formed the Early Detection Research Network (EDRN), a consortium of government, academic, and private-sector institutions focused on developing, evaluating, and validating biomarkers for early cancer detection and risk assessment. Today, the more than 300 researchers and 40 institutions that make up the EDRN are at the forefront of technology-driven research on the use of biomarkers for the early detection of cancer.

NCI is funding many laboratories that develop biomarkers, including several overseas. One example is the laboratory of Dr. Zvi Livneh at the Weizmann Institute of Science in Rehovot, Israel. This laboratory is investigating whether detecting lower-than-normal activity of DNA repair enzymes in blood cells can be used as a biomarker for lung cancer risk in smokers. Another example is the laboratory of Dr. Bruce Robinson of the University of Western Australia in Perth, Australia. This laboratory has identified a novel protein that shows promise as a biomarker for mesothelioma. Work performed in Dr. Robinson's laboratory is part of a multicenter study that will evaluate and validate several biomarkers for this deadly disease.

Once biomarkers are identified, they must be validated and undergo testing in large clinical trials with human participants. Ultimately, the lab tests that result from EDRN research will be added to the clinician's toolbox to aid in cancer prevention and in early therapeutic intervention.

The Web site for the EDRN is located at http://edrn.nci.nih.gov/.

Dr. Zvi Livneh
Dr. Zvi Livneh
Dr. Bruce Robinson
Dr. Bruce Robinson

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