Highlights of Cancer Research Progress
One of every two men and one of every three women in the United States will develop some type of cancer over the course of their lives.
Approximately 8.4 million Americans have a history of cancer.
The consequences are enormous:
Nearly 25 percent of all deaths in our country are due to cancer.
Cancer is the second leading cause of death in the U.S., ranking behind only heart disease.
Medical care expenses for cancer patients and survivors add up to $60 billion
annually, about five percent of all dollars spent on health care in the U.S.
The toll in pain, suffering, and loss of productivity and income is less easily
measured, but keenly felt by the more than one million patients newly diagnosed with
cancer each year, their families, and communities.
There is some encouraging news, however. Figures reported in the most recent Annual Report to the Nation on the Status of Cancer show that from 1992 through 1998, cancer incidence rates declined in men and cancer death rates declined in both men and women. This promising trend is due to the earnest efforts and ardent determination of so many in our country to find better ways to prevent and more effectively treat cancer in all its forms.
Recent advances reported here provide snapshots of a few of the thousands of research projects that NCI sponsors each year that together bring us ever closer to reaching our goal to achieve a future when all cancers are uncommon and easily treated.
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Preventing and Controlling Cancer
Cigarette Promotions Influence Smoking Among Youth
In a study of nearly 500 elementary and high school students in Vermont, researchers explored whether promotional activities for tobacco influence the smoking behaviors and beliefs of adolescents. Results of the study suggest that exposure to tobacco marketing does influence youthful attitudes and beliefs about smoking.
Investigators found that the likelihood that adolescents will start smoking increases after they acquire cigarette promotional items such as hats or t-shirts with tobacco company logos. These findings underscore the harmful effects on adolescents of tobacco advertising and suggest that eliminating cigarette promotional campaigns could reduce adolescent smoking.
Personality Variables Predict Adolescent Smoking
A group of scientists recently determined that better understanding the personality characteristics of adolescents who become smokers can provide key insights for designing effective prevention strategies. These investigators evaluated more than 3,000 fifth graders for factors such as a propensity toward rebelliousness, risk-taking behavior, problem-solving abilities, and susceptibility to peer compliance and approval.
Following up with the students at the end of high school, investigators found that rebelliousness and risk taking had the strongest predictive value for future smoking behavior. In light of these findings, the researchers suggested that smoking prevention programs should address the needs and expectations of rebellious and risk-taking youth and should begin no later than fifth grade.
Learn more about NCI's research on tobacco.
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Experts Recommend Continuing Promotion of Fruit and Vegetable Consumption
An outside panel of experts recently evaluated NCI's decade-long efforts to encourage Americans to include at least five servings of fruits and vegetables in their daily diets through the Five A Day Program.
After considering the science underlying the program, its implementation, and accomplishments, the group recommended that it continue under NCI's leadership while partnering more closely with other NIH institutes, Federal agencies such as the Department of Agriculture and the Centers of Disease Control and Prevention, and the produce industry.
In addition, the evaluation report recommends that NCI continue and expand monitoring of fruit and vegetable consumption in the U.S. as well as its research in related areas such as cancer communications, behavior change, and the mechanisms by which fruit and vegetable consumption reduce cancer risk.
Detecting Cancer
New Technology May Improve Lung Cancer Detection
A major obstacle to understanding and treating the abnormal lesions that are the first sign of lung cancer is that they are often not visible with bronchoscopy, a technique by which physicians use a thin, lighted tube to examine the lungs. Some clinicians have reported, however, that bronchoscopy using ultraviolet (UV) light fluorescence may be a more sensitive technique for detecting these lesions.
In an effort to explore this question, investigators in an NCI-funded Specialized Program of Research Excellence (SPORE) in Lung Cancer carried out the first controlled trial comparing the two techniques. Both approaches tended to pick up irregularities that were not associated with disease, but scientists found that UV fluorescence was more than four times as likely as white light bronchoscopy to correctly identify precancerous lesions.
Spiral CT is a promising new technique that can be used to detect lung cancer at a very early stage, before it has had a chance to spread. This technique uses X-rays to scan the entire chest quickly, in 15 to 20 seconds, during a single breath-hold. It is safe — the amount of radiation during a spiral CT scan is about the same as that absorbed during a mammogram — and simple. But will detecting these early tumors reduce the likelihood of dying from lung cancer?
The NCI is working to find out. The year-long Lung Screening Study (LSS), began in the fall of 2000 to gauge the feasibility of a larger, more definitive study down the road. Through the LSS, we will learn, first and foremost, whether smokers will be willing to be randomized to receive something other than a spiral CT scan in a comparative study. The LSS will also provide important information about the medical follow-up of people who have the scans, as well as the costs involved.
The Lung PRG, whose report (http://prg.cancer.gov/lung/finalreport.html) was released in August 2001, discussed the topic of screening extensively, calling for the rapid evaluation of spiral CT as a means of detecting cancer early and ultimately reducing deaths from lung cancer.
Learn more about NCI's research on cancer imaging
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Genetic Testing of Stool Samples Detects Most Colorectal Cancers
Because colorectal cancer cells are shed into the stool, testing stool samples can be an easy and non-invasive way to detect colorectal cancer.
Exploring this opportunity, one team of investigators has shown that in the majority of patients, colorectal cancers can be detected by screening stool samples for the presence of three genes with tumor-associated alterations - TP53, K-RAS, and BAT26. More studies now are needed to determine the specificity of these genetic tests for detecting colorectal cancer in patients without symptoms.
Learn more about initiatives in early cancer detection
"Optical Biopsy" Provides a Less Invasive Method for Detecting Cancer
Another investigator is developing an imaging technique that may permit patients of the future with certain types of cancer to undergo "optical biopsies," allowing their physicians to diagnose or rule out cancer without the need for tissue samples.
Using a technique known as optical coherence tomography (OCT), scientists have been able to capture ultra-high resolution images of esophageal and gynecologic tissues, allowing them to identify cancerous lesions in these sites. Other organs and surfaces that may be imaged with OCT include the gastrointestinal system, the bladder, the lungs, and skin.
In the future, health care providers may be able to improve diagnosis and treatment by attaching catheters and endoscopes to OCT instrumentation, sparing patients the added time and pain associated with more invasive procedures.
Learn more about NCI's research on cancer imaging.
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Proteomics Offers Hope for New Prevention, Detection, and Treatment
NCI has teamed with the Food and Drug Administration to create a Clinical Proteomics Program. Proteomics is the systematic study of protein expression and function and an important next phase in our pursuit of molecular medicine.
Proteins comprise the functional machinery of the cell, linking circuits and pathways that transmit information within the cell and the entire organism. In cancer, alterations in genes usually cause defects in the corresponding proteins, disrupting the normal communication network of the cell. Using proteomics, cancer researchers are discovering and characterizing disruptions in the protein communication networks that drive the growth and spread of cancer, knowledge that will advance early detection, prevention, and drug development.
For example, a group of NCI scientists has discovered more than 130 proteins that are altered during the transition from benign to malignant disease in breast, ovarian, prostate, and/or esophageal cancers. With additional research, these proteins may serve as early cancer biomarkers or offer possible targets for therapeutic drug development.
Other NCI investigators have developed protein microarrays of key proteins in signal pathways. With this approach, the researchers have determined the process of apoptosis, or programmed cell death, becomes suppressed very early in cancer development.
Center of Excellence Advances Ovarian Cancer Biomarker Discovery
The earlier ovarian cancer is treated, the better a woman's chance for recovery. Currently, most ovarian tumors are diagnosed after they have advanced beyond cure, spurring researchers to look for reliable, minimally invasive techniques for earlier detection.
For example, tumor markers that can be measured in blood or used in combination with imaging may allow health care providers to detect ovarian cancer sooner. Scientists in an NCI-funded Specialized Program of Research Excellence have conducted an extensive search for genes that play a role in ovarian cancer and identified a number of genes never before associated with this cancer. These include mesothelin, HE4, ESE-1, SLPIa, and GPR39.
Scientists now are studying the molecules associated with these genes to determine whether they can be useful as early detection markers. If so, and tests can be developed to detect these markers in blood, this research could have a significant impact on women's ability to survive ovarian cancer.
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Treating Cancer
New Initiatives Aim to Improve BreastCancer Treatment
The findings of clinical trials in breast cancer over the last ten years have provided physicians and their patients with a wealth of new information to guide their treatment choices – but at the same time, have also complicated their decision making.
To help oncologists and patients choose between radiation therapy, chemotherapy, or hormone therapy to try to eliminate cancer cells left behind after surgery, NCI co-sponsored a consensus conference at the end of 2000 to synthesize the information from recent research and make recommendations for routine cancer care. The breast cancer experts participating in the conference provided advice on the factors that should guide the choice of adjuvant therapy, as these follow-up treatments are known, and made recommendations about which patients should consider hormonal, chemotherapy, or radiation therapy. In addition, consensus conference participants also considered the side effects and quality of life experienced by patients undergoing the various forms of adjuvant therapy and promising new directions for this research.
In other research, NCI is sponsoring clinical trials to compare the effects of removing only one or a few lymph nodes during breast cancer surgery to the standard, more invasive practice of removing more lymph nodes.
Breast-Conserving Therapy Is At Least As Cost Effective as Mastectomy
The choice of treatment for breast cancer depends on many factors, including the size and stage of the tumor, a woman's age, other medical conditions, and costs. In a study of nearly 1,700 breast cancer patients 35 and older with early-stage breast cancer, researchers compared the cost of care for mastectomy with that of breast-conserving therapy (BCT).
At six months after diagnosis, the medical care costs associated with BCT were higher than for mastectomy. The cost difference disappeared over time, however, and by five years after surgery, the medical care costs of BCT were less than those for mastectomy, possibly due to the expenses associated with the higher complication rates of mastectomy or later surgical reconstruction of the breast.
This study suggests that breast-conserving therapy is at least as cost-effective as mastectomy and should be weighed equally in treatment considerations about cost. The larger lesson, however, is that short-term and longer-term expenses associated with cancer care may be quite different, and that both considerations should inform health care policy decisions.
New Drugs Provide Hope for Prostate
Cancer Patients with Bone Metastases.
When prostate cancer spreads, it often invades the bones, where it causes severe, debilitating pain. However, several drugs currently under study may combat bone metastases, slowing the spread of the cancer and improving the patient’s quality of life.
For example, the class of drugs known as bisphosphonates has already been established as effective against breast cancer and multiple myeloma, but these drugs have not been considered particularly effective against prostate cancer — until now. Clodronate, a bisphosphonate, has shown activity against prostate cancer metastasis, opening the door for further studies involving more potent bisphosphonates, or higher doses of the drug. A second drug, Atrasentan, targets the protein endothelin-1, which promotes cell growth in bone and which is overactive in prostate cancer cells. Finally, a combination of chemotherapy and a bone-targeted radiation drug, strontium-89 (Sr-89), may prolong the lives of men with prostate cancer that has spread to the bones. Sr-89 is a radioactive substance used to relieve bone pain caused by metastatic prostate cancer. When injected by vein, Sr-89 moves into bones and delivers radiation directly to cancer that has
spread there. Metastasis was a key topic of interest for the Prostate Cancer PRG, whose report is found at http://prg.cancer.gov/prostate/finalreport.html
Phase I Trials Suggest Vaccines for Lung and Colon Cancers
Although the idea of treating cancer with a vaccine that stimulates the body's immune system to kill tumors is generating exciting results for several cancers, success with lung and colorectal cancers has been more elusive. Recently, scientists have taken a new approach that has produced promising results in a Phase I clinical trial.
Researchers first isolated from tumor tissue a portion of carcinoembryonic antigen, a protein usually found only in fetal tissue but abundantly expressed in non-small cell lung, colon, and other cancer cells. They next delivered the isolated antigen to the immune system using an innovative method that seems to heighten the immune response. Researchers hoped that vaccinated patients would produce antibodies to attack the novel antigen and consequently the tumor cells that express it.
Five of the twelve patients in the study did respond to the vaccine, two with dramatic tumor regression. These are promising findings for a Phase I trial, and if more extended clinical trials demonstrate its effectiveness, this approach could lead to a new therapy for lung, colorectal, and perhaps other cancers.
Learn more about NCI's clinical trials.
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Early Hairy Cell Leukemia Trial Results In Complete Remissions
A new immunotherapy for hairy cell leukemia, a cancer of the immune system, has produced impressive results in a preliminary clinical trial. The treatment works by using a specially designed molecule known as BL22 to deliver a deadly toxin directly to the hairy cell leukemia cells.
Scientists made BL22 by joining portions of an endotoxin made by the bacteria Pseudomonas aeruginosa with an antibody that recognizes and binds to CD22, a protein found on the outside of hairy cell leukemia cells. BL22 is a small molecule designed to get to the tumor quickly and with less toxicity to the body. When BL22 reaches its target, the cancer cell internalizes the deadly toxin by natural mechanisms and dies.
Of the 16 patients with hairy cell leukemia who participated in this preliminary trial, 11 experienced complete remission and another two partial remission after BL22 immunotherapy. These early clinical results show promise for BL22 treatment of hairy cell leukemia and other cancers that express CD22.
Metastatic Melanoma Patients Experience Regression with Immunotherapy
Melanoma is the most rapidly increasing cancer in the United States and is virtually lethal once it has spread beyond the initial site. Recent metastatic melanoma studies provide some of the first examples of the successful application of specific immunotherapy for human cancer based on an understanding of the molecular basis of the immune response against the disease.
For example, many patients vaccinated with gp100 melanoma antigen found on the outside of melanoma cells, have produced immune cells that attack their cancer. In a preliminary trial, one-third of all metastatic melanoma patients experienced tumor regression when this vaccine was administered along with the immune stimulating cytokine, Interleukin-2 (IL-2). (IL-2 is produced by certain white blood cells and can help boost immune response.)
Patients are experiencing substantial tumor regression in pilot studies of vaccination with a number of other antigens characteristic of melanoma cells, without the help of IL-2 or other immune boosting cytokines.
In recent studies, some of the cancer attacking immune cells were removed from patients and allowed to increase in number in a laboratory culture. Transferring larger quantities of the immune cells back to the patient resulted in additional cancer regressions. Researchers have begun exploring molecular and genetic characteristics of antigens for breast, ovarian, prostate and lung cancers, and similar treatment approaches are being applied to forms of these cancers.
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Understanding Cancer and its Causes
Tumor Growth May Be Stopped By Depriving Cancer Cells of Oxygen
One strategy for stopping tumor growth is to selectively starve cancerous tissue for oxygen. Angiogenesis refers to the body's ability to grow new blood vessels , a process necessary for normal activities in the body as well as for tumor growth. If we learn how to stop this process, we should be able to arrest tumor growth.
Scientists have learned that the mammalian cell uses the protein hypoxia-inducible factor (HIF) to help turn angiogenesis on and off. When HIF is present, it turns on the genes that start the angiogenesis process. At normal levels of oxygen the cell has a mechanism that continuously breaks down HIF. During hypoxia, such as occurs during tumor growth, another mechanism makes a small change to the structure of HIF so that it is resistant to degradation. HIF levels increase, blood vessels grow, and the new tumor thrives.
Scientists are searching for possible drugs to target the HIF oxygen sensing and signaling pathways to stop angiogenesis without harming healthy cells.
Reversing the Silence of a Gene May Make Cancer Therapy Effective
Neuroblastoma is the most common solid childhood tumor outside the brain area. Despite major advances in cancer chemotherapy and bone marrow transplantation, the long-term survival rate for children with aggressive forms of this disease remains very low.
Cancer geneticists are working on a new treatment idea based on a recent finding about the gene capsase 8, which may be involved in a set of difficult to treat neuroblastoma cases. In these neuroblastomas, capsase 8 does not do its job, because it is either missing or is chemically altered and rendered silent by a DNA methylation process. Scientists found that neuroblastoma cells without capsase 8 activity grown in the laboratory are protected against a number of cancer therapy drugs directed against DNA targets.
Researchers are now studying the possibility of using demethylation agents to reverse the chemistry that silences capsase 8, thus rendering the neuroblastoma cells susceptible to the chemotherapeutic agents.
No Connection Found Between Cellular Telephone Use and Brain Tumors
The use of hand-held cellular phones involves placing a small transmitter that emits radio frequency radiation next to the head. Given the unknown cancer risk posed by this radiation and the important public health implications, NCI scientists included cell phone use in a comprehensive study on the causes of brain tumors.
Approximately 800 adult brain tumor patients and 800 controls (adults without brain tumors) from three medical institutions in the United States were questioned about their cell phone usage. Researchers found that regardless of years of use or number of minutes of use per day reported, there was no increased risk of brain tumors for cell phone users compared to non-users. Brain tumors also did not occur more frequently on the side of the head on which cell phone users reported holding their phone.
While the NCI study (1994-1998) was conducted at a time when analogue phones were primarily used, there is no evidence at this time that cancer risk differs for the higher frequency digital phones more commonly used today.
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Scientists Identify Chemosensitive Gliomas
Gliomas are malignant tumors of the brain that arise from glial cells, a type of cell that provides support and insulation for neurons of the brain. Most are quickly fatal despite treatment, but the prognosis depends heavily on the specific type of glioma. Patients with oligodendroglioma, for example, respond well to combined treatment with the drugs procarbazine, lomustine, and vincristine with approximately two-thirds experiencing long-term remissions.
Only recently, however, have scientists begun to identify which patients would respond to the combined treatment. Scientists are learning how to predict response based on the genetic mutations present in the glioma tissue. For example, patients with altered portions of chromosome 1 and 19 tend to respond much better to chemotherapy than those with mutations in the genes PTEN, EGFR, and CDKN2A.
This research will improve the ability of physicians to recommend appropriate treatment for patients. Patients with responsive tumors will increase their chances of survival when they are treated earlier. Other patients may be spared ineffective and toxic chemical treatments and offered alternative therapies.
Racial and Ethnic Differences in Prostate Cancer Need Further Study
The Prostate Cancer Outcomes Study is following over 3,000 men to learn more about the results of different therapies and their effect on quality of life. One recent report drawing on data from the study examined racial and ethnic differences found among men who developed advanced prostate cancer.
Researchers found that African American men have the greatest risk of developing advanced disease (12.3 percent of study participants). This rate is higher than that of Hispanic men (10.5 percent) and about twice that of non-Hispanic Whites (6.3 percent). Differences in socioeconomic status, symptoms, and tumor characteristics seem to account for the differences between non-Hispanic Whites and Hispanics, but do not explain a significant portion of the African American disparities.
Investigators suggested that further research on biologic markers, genetic susceptibility factors, and additional socioeconomic factors such as use of health care systems, distance from health care, diet, literacy, and health beliefs is needed to sufficiently describe these disparities.
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Mouse Models of Human Cancers Consortium:
Modeling Human Cancers in the Mouse
About Mouse Models
How Mouse Models Are Advancing Cancer Research
The Future of Mouse Models
About Mouse Models
Animal models - laboratory animals that have specific characteristics resembling a human disease or disorder - play an invaluable role in cancer research. Technologies available today allow scientists to create animal models of cancer by transferring new genes into animals or inactivating certain existing genes. This makes the animals susceptible to specific cancers via the same genetic and environmental factors that affect humans. With these models, scientists can:
- Study the biological changes associated with every stage of tumor development.
- Test new approaches to detection and diagnosis.
- Evaluate prevention and treatment strategies.
For a variety of reasons, mice are particularly well suited for cancer research. To start, mice and humans are similar in their genetic makeup and susceptibility to cancer. As a result, the development of tumors in mice largely parallels that in humans. Further, mouse tumors develop over the course of months rather than the years usually required for cancer to develop in larger animals and humans.
But the complexity of cancer makes the development of mouse models a far more challenging task for cancer than for some other diseases.
Fortunately, cancer researchers today have a wide range of resources to bring to bear on this task. Scientists have access to:
- Increasingly detailed databases containing the details of mouse and human genes
- A growing body of information on the molecular characteristics, or signatures, of tumors
This expanding knowledge - coupled with tools for modifying the genes of laboratory mice and a battery of tests to identify relevant cancer genes and proteins - ensure that cancer mouse models parallel the development, progression, and clinical course of human cancers.
Created by NCI in late 1999, the Mouse Models of Human Cancers Consortium involves 20 multidisciplinary groups of investigators in improving the pace and efficiency with which mouse models of cancer are developed and tested, and to ensure they are readily available to scientists. Consortium scientists are working to develop and evaluate mouse models for breast, prostate, lung, ovary, cervix, pancreas, skin, blood and lymph system, colon, and brain cancers.
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How Mouse Models Are Advancing Cancer Research
Throughout the Consortium and in other NCI-supported laboratories, researchers are using mouse models to examine the interplay of genetic and environmental factors in cancer susceptibility, test novel approaches to detection, diagnosis, and imaging, and advance the use of genetically engineered mice for prevention, therapy, and population research.
Gene-Environment Interactions
Cancer Detection and Diagnosis
Cancer Therapy
Cancer Imaging
Gene-Environment Interactions
Mouse models provide a unique opportunity to explore how genetic and environmental factors interact to give rise to cancer. With such models, scientists can test the effects of a particular chemical in a controlled environment using animals with a known genetic makeup.
For example, researchers are using a recently developed mouse model of lung cancer to:
- Investigate the role that genetic factors play in determining why some smokers develop lung cancer and others do not.
- Test whether tobacco smoke accelerates tumor formation.
- Define the genes that confer susceptibility to tobacco-related cancers.
Cancer Detection and Diagnosis
Because samples of human cancers at their earliest stages can be difficult to obtain, mouse models also are invaluable in cancer detection studies. Tumors in these mice can be examined to verify the role that each genetic alteration plays in causing cancer and in its progression, and may also reveal changes informative to human cancer diagnosis or early detection.
An example of this type of research is a newly developed mouse model that closely mimics inflammatory bowel disease, a condition associated with increased cancer risk. Researchers are using this model to test the effect of known and suspected causal factors - such as the Helicobacter bacteria - on the timing and severity of cancer. By taking biopsies at varying times after infection, they are looking for the earliest changes indicating increased risk for gastric, intestinal, or colon cancer.
Cancer Therapy
Defining the changes associated with cancer also is fundamental for finding potential targets for early intervention. Once these targets have been identified, scientists depend on mouse models to test the efficacy of new drugs, and to understand why a drug does - or does not - work as expected. Indeed, one of the most important roles of mouse models is in the development of drugs to treat cancer.
In one recent example of using mouse models to test treatments, investigators used a model of one type of childhood leukemia to help solve the mystery of why some children respond to the standard therapy of retinoids while others do not. As they studied the problem in the model, scientists discovered that the mice that did not respond to treatment had an unexpected gene rearrangement. With this information, the researchers then developed a new treatment that blocks the action of the rearranged gene. It was effective in combination with retinoids in mice, and these investigators are now assessing the combined treatment in childhood leukemia patients who do not respond to retinoid therapy alone.
Models also are valuable for studying a host of treatment questions, such as determining mechanisms of drug resistance and defining new treatment targets.
Cancer Imaging
With specialized equipment and techniques for imaging mice and other small animals, investigators are using mouse models to explore improvements in cancer imaging and treatment in order to determine whether anti-cancer drugs have reached their targets and to track response to therapy. Since 1999, much of this research has been fostered by Small Animal Imaging Resource Programs that NCI has established at a number of research centers around the country.
As Consortium investigators develop more mouse models of cancer, collaborations among them and small animal imaging specialists are expected to grow. Already, Consortium scientists involved in developing mouse models for prostate cancer have teamed with colleagues from the NCI-funded Small Animal Imaging Resource Program to use positron emission tomography imaging to study prostate cancer development, from its beginnings in the prostate to its metastasis (spread) to bones and other organs.
Similarly, investigators testing mouse models of brain tumors are collaborating with small animal imaging experts to use magnetic resonance imaging to test approaches to gene therapy for brain tumors. Experiments of this kind are already revealing new avenues for human therapy.
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The Future of Mouse Models
If the research community is to employ mouse models to their greatest advantage, extensive collaborations are needed among those who can best inform the design of the models and their ultimate use in cancer research. NCI is facilitating the formation of collaborative groups - e.g., for ovarian, brain, pediatric, and pancreatic cancer modeling - to ensure rapid incorporation of human cancer research discoveries into mouse model design and application.
With NCI's help to organize conferences and symposia, Consortium investigators are spearheading the dissemination of information about:
- Mouse engineering tactics
- Development of validation standards for cancer models
- The practical application of models to inform many aspects of cancer research
The achievements of Consortium investigators and the need to deploy models to the research community prompted NCI to establish the Mouse Models of Human Cancers Consortium Mouse Repository, to which interested scientists are invited to contribute models.
When it opened in February 2001, the NCI repository had three mouse strains available for distribution. The number of mouse models offered is expected to quickly increase, reaching at least 30 by early 2002. NCI will expand the repository in the future to accommodate the growing requirements of the cancer research community for well-designed and thoroughly tested mouse models.
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CGAP Is a Gateway to New Exploration and Discovery
NCI's Cancer Genome Anatomy Project (CGAP) was established in 1997 to determine the gene expression profiles of normal, precancer, and cancer cells and to provide public access to this information for all cancer researchers.
The project is now providing:
- A wealth of human and mouse genomic data
- Informatics tools to query and analyze the data
- Information on methods
- Access to biologic materials developed through the project
With public data and analysis tools, researchers can now find "in silico" answers to biological questions in a fraction of the time it used to take in the lab.
Researchers have started mining the CGAP databases and are:
- Discovering new, potentially cancer-causing genes
- Identifying candidates for molecular targeting research
- Helping to build microarrays for cancer cell signature research
For example:
- Because cancer is such a complex disease, finding the many cancer-causing genes involved and understanding their role is crucial to developing new treatments to combat the disease. Cancer researchers at Duke University Medical Center, in collaboration with CGAP, examined the expression of more than 24,000 genes in the oxygen-deprived (hypoxic) cells of glioblastoma multiforme, a form of brain cancer. They identified ten genes believed to play a significant role in allowing this tumor to thrive under hypoxic conditions. Scientists are working to find the function of these genes with the long-term goal of developing targeted inhibitors that may be used in formulations against the cancer.
- Until recently, diffuse large B-cell lymphoma (DLBCL) had been traditionally classified as a single cancer, but patients suffering from this disease show diverse responses to chemotherapy. Only 40% of patients respond well to treatment, while the remainder succumb quickly to the disease. Using CGAP data, NCI and NCI-supported scientists developed a microarray called a lymphochip that contained 18,000 genes, which included those preferentially expressed in lymphoid cells as well as in cancer and the immune system. The expression analysis showed that DLBCL can be categorized into two distinct classes that broadly correlate with the clinical outcomes.
These results have already begun to contribute to our goal to improve detection, diagnosis and treatment of cancer. Since these discoveries come from early application of CGAP resources, CGAP's impact on the future of cancer research and clinical advances promises to be substantial.
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Results Show Value of SPOREs
Since their start in 1992, NCI's Specialized Programs of Research Excellence (SPOREs) have grown to include 27 centers focused on translational research for breast, lung, gastrointestinal, ovarian, prostate, genitourinary, and skin cancer.
Recent advances testify to their value:
- The discovery that smokers who carry certain gene types are less likely than others to successfully quit. This finding raises the possibility that specially tailored cessation programs may help these smokers.
- A better approach to detecting the early signs of lung cancer. Investigators found that the use of fluorescent light in bronchoscopy dramatically improved physicians' ability to identify the early signs of lung cancer.
- Confirmation that family clusters of pancreatic cancer have a genetic basis. After tracking relatives of pancreatic cancer patients since 1994, researchers recently confirmed that those with two or more relatives with pancreatic cancer are at higher risk for the disease. This finding provides important information for these relatives and their physicians and supplies scientists with a vital first step toward identifying the responsible genes.
- Promising results in an initial clinical trial of a treatment vaccine that stimulates the immune system of pancreatic cancer patients to take action against their tumors. Investigators have now expanded testing of this new treatment to a larger number of patients.
- Confirmation that variations in the molecular profiles of different types of breast tumors can yield important clues about the prospects for relapse and long-term patient survival. Other SPORE investigators studying breast cancer reported encouraging results from their studies of ductal lavage, a new approach to early breast cancer detection.
In the coming years, the program will continue to establish centers on the cancers currently under study while expanding to include centers devoted to every major cancer site.
View the proposed schedule for expansion
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SEER Increases Coverage and Forms Partnerships
Cancer intimately touches the lives of perhaps every American at some point, whether as a patient, a loved one or a caregiver. NCI expanded its Surveillance, Epidemiology, and End Results (SEER) program in 2001 to better understand the cancer burden across the full spectrum of the U.S. population.
- New coverage in four states - Louisiana, Kentucky, New Jersey, and California (the remaining portions of the state not already included) - increases overall surveillance from 14 to 26 percent of the U.S. population, from about 35 million to over 65 million people.
- These additions increased coverage of several populations that were previously underrepresented, including African Americans, Hispanics, American Indians, Alaskan Natives, Asian and Pacific Islanders, low-income Whites in rural areas and other areas of high poverty, and regions with high cancer death rates.
Learn more about SEER registries
Several partnership activities with state registries, which capture a wealth of information not directly covered by SEER, have also broadened SEER surveillance. For example:
- NCI, CDC, and the California State Department of Public Health collaborated to plan specialized cancer control strategies geared toward reducing the local cancer burden. They used a survey to collect health data and local health systems and policy measures from diverse ethnic, social, and cultural communities in California. This standardized data can be used in developing local cancer control programs and will allow comparison with national cancer control data, providing insight into the direction of future cancer trends.
- NCI, CDC, and other partners are working to establish guidelines that address the technical difficulties of sharing data between state and Federal registries, such as differences in the types of data each registry collects and how the data is stored. Simpler, standardized rules will enable better comparability among data sets and increase opportunity for collaboration.
- NCI is working with others to develop computer applications that will be able to pool and analyze data from multiple cancer registries and disseminate the findings to the cancer community.
The more we can share surveillance data among state and national agencies and the more data we can amass through broader coverage of the U.S. population, the better picture we will have of the cancer burden in the U.S. and the better equipped we will be to find ways to reduce that burden.
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