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. |
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.
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.
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 |
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.
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 (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.
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.
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. Bruce Robinson |
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