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Research: Cause, Prevention, Detection and Treatment

Within the past three decades, major progress has been made in curing the cancers that affect children and young adults. Researchers now understand in minute detail many of the processes that transform a normal cell into a malignant one, and this knowledge will eventually allow us to identify molecular targets and design customized prevention and therapeutic strategies. Nevertheless, as the population ages, cancer remains a formidable threat to the lives of millions of Americans. Basic biomedical research will remain the cornerstone of continued progress in understanding cancer. Without research, our knowledge base will be frozen at its current level. With it, there is a virtual guarantee that many of the cancers that cannot be cured today will be controlled in the future.

Causes of Cancer

Molecular Genetics. This exciting new area originates from the knowledge that all cancer results from genetic defects, mutations either inherited from a parent or occurring during a person's lifetime from exposure to chemicals or radiation. Genetic abnormalities seem to initiate cancer in many different kinds of tissue -- breast, lung, colon, prostate. New cancer-causing genes (oncogenes) and tumor suppressor genes are being discovered every year. Understanding the factors that determine the similarities and differences among various cancers means that eventually we may be able to control any cancer-causing events that might occur. Molecular Epidemiology. Epidemiologists study the links between suspected carcinogenic exposures and cancer occurrence in populations. Increased knowledge of molecular biology can greatly enhance the precision and power of cancer epidemiologic research by providing new tools for measuring levels of exposure and susceptibility in individual persons. Inheritance of cancer susceptibility genes varies widely, as does an individual's ability to handle carcinogens, to respond immunologically, and to repair damaged DNA. Molecular epidemiologic research may make it possible to develop specific cancer risk profiles in particular risk settings. Knowledge of this sort may in turn allow a person to avoid certain occupational and environmental exposures, based on his or her individual risk profile.

Prevention

Chemoprevention. Anti-cancer activity has been demonstrated in a highly diverse group of biological and chemical agents, including: analogs of vitamin A, plant phenolics (green tea), soybeans, anti-hormones, and agents such as aspirin. Their potential has been shown in the laboratory and hopefully will carry over for cancer prevention in people at high risk.

Cancer Vaccines. Advances in understanding how the immune system works have combined with new techniques in molecular biology to make this one of the most promising areas in cancer research today. Preventive cancer vaccines are being developed against the cancers known to be associated with viruses -- cervical carcinoma, liver, and some lymphomas. The majority of cancers are not associated with viral infection, but investigators are probing novel ways to present the tumor-specific proteins (antigens) that will cause the body's own immune system to respond -- a therapeutic "vaccine," to be given after the cancer occurs. Most of the current work involves malignant melanoma, but therapeutic, and potentially preventive, vaccines directed at antigens common to many cancers, such as the carcinoembryonic antigen on breast, lung, and colon cancer, and the prostate-specific antigen are under development.

Detection

New Imaging Technologies. High-quality mammography combined with clinical breast exam remains the only screening method clearly tied to reduction in breast cancer mortality. Lower dose x-rays, digitized computer rather than film images, and the use of computer programs to assist diagnosis, are almost ready for widespread dissemination. Other technologies also are being developed, including magnetic resonance imaging and ultrasound. In addition, a very low radiation exposure technique, positron emission tomography has the potential for detecting early breast cancer.

Biomarkers. The identification and characterization of genetic or biochemical markers in blood or tissues that will detect the earliest changes along the carcinogenesis pathway and monitor the efficacy of various therapies and preventive interventions is a major goal of cancer research. Scientists have identified genetic changes in stool specimens that indicate the stages of colon cancer, and other biomarkers such as gene mutations, hormone receptors, proteins that inhibit metastasis, and enzymes that metabolize drugs are all being used to determine the severity and predict the course of breast, prostate, lung, and other cancers.

Treatment

Gene Therapy. No longer a laboratory phenomenon, gene therapy has moved into early clinical trials. Results obtained in an animal model with a "suicide vector," a virus carrying genetic information that makes the cells it infects susceptible to an anti-viral drug, have been translated into a trial in human brain tumors. Other gene therapies for cancer include transferring genes that increase the patient's immune response to the tumor, or that confer drug resistance to the bone marrow so that higher doses of chemotherapeutic drugs can be given.

Angiogenesis Inhibitors. For tumors to grow and metastasize, they must have nutrients and oxygen brought in by the blood. Tumor cells make factors, such as fibroblast growth factor, that cause the formation of blood vessels (angiogenesis). If this growth of new vessels could be blocked, tumors could not grow beyond the size of a pea. Several compounds that have anti-angiogenesis properties are being investigated.

Rational Drug Design. In the past, cancer-fighting drugs were discovered by "trial and error." Today, determination of the 3-dimensional structure of oncogene products and other important molecules in the cancer pathway can be coupled with mathematical computer models to design compounds to interact specifically with the target molecules. Preliminary studies are underway to create drugs that will inhibit many steps in the cancer pathway_oncogene action, hormone receptors, growth factors, metastasis, and angiogenesis.

Psychosocial and Behavioral Research

Evidence is mounting that lifestyle (tobacco, diet) and socioeconomic and cultural factors influence a person's general health and chances of developing cancer, as well as the mental and emotional ability to cope with cancer if it occurs. We are mindful that perhaps 50% of patients who develop fatal cancer could have been saved had they been able to use existing knowledge about smoking, diet, exercise, and means of early detection.

Research on behavioral modification is having a significant impact on symptoms of cancer and its treatment, such as pain, nausea, and vomiting. Other research deals with stress during treatment and during recovery after surgery or radiation treatment. The response of both patient and family to the disease, the patient's sexual concerns, rehabilitation, employment, and insurance needs, and ways to provide psychosocial support have emerged as important areas of research and clinical care.

Pain is a significant problem for 50%-70% of patients with cancer, but cancer pain can usually be relieved. The patient's own assessment of pain should be used to guide therapy, which needs to be individualized. Analgesics may be given orally or by a variety of other methods, and if needed, should include opioids such as morphine. Patients and families should not hesitate to discuss pain problems with their caregivers.

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