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Extraordinary opportunities in cancer research.

Cancer statistics paint a daunting and seemingly overwhelming picture. One out of every two men and two out of every three women will be diagnosed with cancer during their lives. Nearly 25 percent of all deaths in the United States result from cancer, and medical expenses for cancer cost our nation up to $60 billion a year. With our aging population, the number of people diagnosed with cancer is expected to double from 1.3 million in 2000 to 2.6 million by 2050.

With recent advances in cancer research, however, a comprehensive solution to the problem of cancer is increasingly within reach. The National Cancer Institute (NCI), the federal government's primary organization for cancer research, is in the forefront of that effort. We both conduct and fund research on multiple fronts, from basic laboratory studies to large clinical trials involving thousands of patients. Just as importantly, we strive to close the gap between basic research and the translation of the knowledge that we gain from it into practical help for patients at risk for, diagnosed with, or recovering from cancer.

Perhaps our greatest hope lies in the emerging understanding of cancer at the genetic, molecular, and cellular levels. More than 5,000 NCI investigators, working alone or in groups, have embarked on an incredibly challenging intellectual exercise. Their ultimate goal is to treat each cancer tumor according to its unique genetic and molecular fingerprint.

"The paradigm I grew up with as an oncologist was to find cancer and kill it," said NCI Director Andrew von Eschenbach. "Now, we look forward not only to eradicating cancer, but also to modulating and altering the behavior of the disease. This new paradigm uses biology-based interventions to detect, treat, and prevent cancers."

In the coming years, NCI will focus much of its efforts on a halfdozen areas that we believe offer extraordinary potential: genes and the environment, cancer imaging, molecular signatures and targeting, tobacco-related cancers, and cancer communications.

GENES AND THE ENVIRONMENT

Exactly how genetic and environmental factors interact to cause cancer remains a complex puzzle. Mutations in some genes, such as that for familial adenomatous polyposis, are so powerful that carriers are almost certain to develop colon cancer. Mutations in other genes, such as BRCA1 and BRCA2, are just some of the many risk factors for breast cancer. Certain environmental factors, such as smoking, are strong but not absolute predictors of cancer.

NCI investigators are working on identifying the cancer risks associated with the interaction between certain environmental exposures and genetic factors. With this better understanding, we can check genetic susceptibility, identify treatments for people at high risk, and develop strategies to avoid adverse exposures. We are also working toward more patient-friendly tools, with such non-invasive methods as screening for lung cancer by sputum samples or sampling DNA from cheek cells.

Various ongoing studies are helping to build the large databases needed to formulate prevention and treatment options. Currently, we are collecting not only data on environmental exposures, but also actual tissue, blood, and other body-fluid samples from some 700,000 study participants. Because genes play such a significant role in the development of cancer, we are tracking cancer trends among 14,000 families enrolled in cancer registries that record family history, demographics, and lifestyle risk factors.

This past summer, NCI reported its findings on a lengthy study -- a decade-long investigation into possible environmental causes of elevated breast-cancer mortality rates in Long Island, NY, and surrounding areas. Researchers looked at the current and past exposure of 1,508 local women to contaminated drinking water; air pollution, electromagnetic fields, and other suspected hazards. The study found a negligible connection. There was some increased cancer risk with exposure to pollutants such as cigarette smoke and diesel fuel, but not with other factors such as exposure to pesticides. The project continues with more than a dozen follow-up investigations into the roles played by various genes, lifestyle choices, and contaminants in the development of breast cancer.

CANCER IMAGING

During the past twenty-five years, imaging technology has advanced from x-ray studies to such recent breakthroughs as virtual colonosocopy, where computerized tomography (CT) is used to scan for colon cancer. NCI investigators also are conducting research into such technologies as "smart contrast agents." Injected into the body, the agents change shape and become fluorescent when they come into contact with certain enzymes present in cancers. One new contrast agent in the pipeline enhances PET imaging by targeting elevated levels of an enzyme present in prostate and other cancers. Sophisticated imaging techniques are also proving vital in determining the effectiveness of cancer drugs specifically designed to prevent the growth of blood vessels that feed tumors.

Several large clinical trials are now underway to evaluate and refine new imaging technologies. In September 2002, the National Lung Screening Trial (NLST) began enrolling 50,000 current and former smokers in a study comparing the use of spiral CT to standard chest X-rays in reducing deaths from lung cancer. Both methods have been used to find lung cancer early, but so far neither method has been shown to reduce a person's chance of dying from the disease. The trial should determine which one imaging tool best reduces a person's chances of dying from lung cancer.

"Lung cancer kills more people than cancers of the breast, prostate, colon, and pancreas combined and will kill more than 155,000 people this year," says the NLST project officer, Dr. John Gohagan, of NCI's Division of Cancer Prevention. "Our hope is that this study will lead to saving lives among the 90 million current and former smokers in the United States.

MOLECULAR SIGNATURES

NCI is expanding research into molecular signatures, or learning how small changes in only a few genes or proteins can disrupt cellular functions and allow cancer to develop. Such knowledge will help diagnose cancer at an earlier stage, help tailor treatments, and help monitor patient recovery.

This effort is resulting in some exciting new technologies. For example, this year work should be completed on a Cancer Chromosome Aberration Map, a genetic map that defines distinct alterations in chromosomes that lead to cancer. NCI makes this and other genetic resources, such as tissue repositories, readily accessible to researchers worldwide.

The discovery and use of biomarkers, or substances in body fluids and tissues that indicate the existence of tumors, are leading to new advances in the early detection of cancer. This past summer, scientists working on a joint NCI and Food and Drug Administration study announced success with a new, thirty-minute test that detects ovarian cancer from proteins found in blood samples.

This new technology combines proteomics -- the study of proteins inside a cell -- with artificial-intelligence computer programs. Using simple finger-prick blood samples, a computer has correctly identified a pattern of just a half-dozen or so proteins, among thousands found in a person's blood, that correctly identified the presence of ovarian cancer. This process has now been expanded to test for prostate cancer, and in the future, may be used to diagnose other cancers.

MOLECULAR TARGETING

Research is also entering a new era of molecular targeting, where drugs are designed to target specific molecular features of a cancer cell while sparing healthy tissue. NCI is encouraging this development by supporting more than forty research groups working in this area. One group is exploring an aberrant protein that enables cancer cells to evade apoptosis, or the natural death that comes to damaged cells. Others are examining proteins found in unnaturally high levels among cancer cells to determine what role they play in cancer growth.

NCI is taking that vital next step by translating discoveries made in laboratories for use in the clinical care of patients. One novel gene-therapy approach currently being tested delivers a pair of therapeutic "suicide genes" to prostate tumors. The genes sensitize malignant cells to specific cancer drugs and radiation.

Another new approach is to replace a patient's immune system with cancer-fighting cells that aid in shrinking tumors. Certain immune cells taken from a patient's tumor, then grown and strengthened in the laboratory, are injected back into the patient's body to attack cancer cells. This experimental technique, known as adoptive transfer, has shown promising results in patients with metastatic melanoma who have not responded to standard treatment. With further research, scientists hope that this approach may have applications to many cancer types, as well as to infectious diseases such as AIDS.

TOBACCO AND CANCER

The devastating impact of tobacco use and tobacco-smoke exposure on the incidence of cancer is as compelling as it is conclusive. Tobacco use is responsible for nearly one in five deaths in the United States. NCI is especially concerned about the health of former smokers, people who have managed to kick the habit yet still comprise about half of the estimated 170,000 lung-cancer patients diagnosed this year.

Lung-cancer studies are a primary focus of much of our research on tobacco-related cancers, but the findings are often applicable to other cancers. As with other cancers, we find that genetic make-up plays a role in not just the progression of lung cancer, but the predisposition to become a smoker. Research has shown smokers with certain genetic traits start smoking almost two years earlier than others, so NCI is studying this genetic predisposition to devise tailored approaches to smoking cessation.

NCI is expanding support for studies that test ways to prevent tobacco use among the young and those willing to quit. With more than fifty research grants in this area, NCI is finding evidence that both social and genetic factors are predictors of tobacco use among youth. One study shows that the optimal age for smoking-prevention interventions is between ten and fifteen years of age, much earlier than most programs target. Another shows that middle schoolers who view more tobacco use in movies are more likely to smoke.

While costly and time-consuming, studies that include genetic and biomarker factors are invaluable in understanding cancer risks and exposures to carcinogens before a diagnosis of cancer. The Prostate, Lung, Colorectal, and Ovarian screening trial, for example, is examining the genetic factors that influence smoking and how genes might be involved in nicotine dependency.

Unfortunately, the best smoking-cessation treatments are effective for fewer than a third of all smokers trying to quit. For that reason, NCI is funding behavioral, pharmacological, and community treatment efforts that tailor interventions to the unique needs of individual smokers. One NCI program providing computer-assisted feedback to smokers resulted in success rates almost 33 percent higher than cessation programs without it.

CANCER COMMUNICATIONS

It is not unusual for today's cancer patients to arrive at their doctor's office complete with printouts of information from NCI's award-winning cancer-information Web site, www.cancer.gov. NCI's Cancer Information Service provides personalized answers to questions about cancer, in English and Spanish, at the toll-free number 1-800-4-CANCER. By providing accurate and easily accessible cancer information, NCI helps to empower patients faced with making decisions about prevention, treatment, survivorship, and end-of-life issues.

NCI is also working towards ending the digital divide with cancer-information programs designed to serve people who frequently lack access to computers. These programs are offered to parents of Headstart students and residents in economically depressed urban and rural areas.

Our NewsCenter Web site, with its downloadable images, audio clips, and press releases, is intended to aid the media in accurately reporting cancer news. Benchmarks, an added feature at this site, reports in detail on emerging technologies in cancer research, such as proteomics and nanotechnology. These sites additionally serve as powerful educational tools for the general public.

To ensure maximum benefits from our investment in research, we are strengthening our partnerships with voluntary health organizations, HMOs, and community-health practitioners. One such joint project is testing a new smoking-cessation program for older smokers. It includes a written, evidence-based guide tailored to smokers fifty and older, as well as one for Spanish-speaking Medicare beneficiaries.

While the focus and methods may change as science evolves, NCI remains committed to reducing cancer's terrible burden on our nation and its citizens. By building on these areas of extraordinary opportunity, we hope to achieve our vision of a future where all cancers are uncommon and treatable. With the courage of our cancer-research and care community, and continued strength of our resources, hope is stronger than ever that the years to come hold promise beyond our imaginations

Peggy Vaughn is a press officer in the Press Office of the National Cancer Institute in Bethesda, Maryland.
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Author:Vaughn, Peggy
Publication:Phi Kappa Phi Forum
Geographic Code:1USA
Date:Jan 1, 2003
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