Thirty years ago America's president declared "war on cancer." This year, in the US alone, 1,500 men, women and children lose their personal battle with cancer every day. When will the war end?
I believe that for many cancers the war will end soon. Thanks to knowledge from basic research, we have new tools with which to attack cancer. These new tools are providing more rapid diagnosis and more effective treatments. They are producing new drugs that target molecular changes unique to cancer cells, making it possible to predict who may be at risk for developing cancer because of genetic or environmental factors. These advances will save many lives.
Cancer affects many different organs and tissues in the body. Although cancers differ greatly in their appearance and behavior, they have a common cause: damage to genes. Genes are chemical coding units that specify the structure and function of our bodies. All the cells in our bodies have the same complement of genes, half from each of our parents. What makes one kind of cell different from another is the combination of genes that are active in each cell.
Genes can be damaged by environmental factors, such as radiation or chemicals. They can also be damaged by the products of normal metabolism. Our bodies have elaborate repair systems that maintain the integrity of our genes, even in the presence of damaging agents. Occasionally, however, damage is not repaired. If the damage occurs in key genes that regulate cell growth, cancer can develop. The repair systems themselves help protect us from cancer. For example, one kind of colon cancer develops more frequently in individuals who have a defect in a system that repairs damaged genes.
Cell growth is regulated by a balance between genes that stimulate growth, and those that inhibit it. Genes that stimulate cell growth are called oncogenes; those that inhibit it are called tumor suppressor genes. When oncogenes are activated, or tumor suppressor genes disabled, cells can multiply out of control. Oncogenes can be activated by mutation (changes in gene structure) or by gene amplification (production of many copies of a gene). Tumor suppressor genes can be disabled by mutation, or by spontaneous loss during cell division. Cancer cells are genetically unstable, that is, they have abnormal numbers of chromosomes, the cellular elements that carry genes. Genetic instability contributes to loss of growth control by producing imbalances in gene activity. Traditionally cancer has been diagnosed by the characteristic appearance of cancer cells observed through a microscope. Increasingly, cancers are identified by their characteristic patterns of gene activity (their "molecular signature"). New techniques, including "gene chips," have made it possible to measure the activity of thousands of genes simultaneously. The molecular signatures can be used to classify cancers more precisely, making them easier to treat. For example, these techniques have been used to identify some kinds of lymphomas (cancers of the blood) that respond well to chemotherapy. Similar techniques have been used to identify genes involved in tumor metastasis.
Some genetic changes are common to many types of cancer, whereas other changes are specific to particular cancers. Dozens of oncogenes and tumor suppressor genes have been identified, providing targets for the development of new anti-cancer drugs. A striking recent example is a drug that targets a molecular change characteristic of chronic myelogenous leukemia cells. The drug is providing an alternative to bone marrow transplantation, the only treatment that was effective previously.
Mutations in certain genes have been found to cause hereditary forms of breast and ovarian cancer. This has made it possible to identify women who may be at high risk because they inherit these susceptibility genes. (Inherited forms of breast and ovarian cancer are only a small fraction of the total.) Close observation and rapid treatment, or prophylactic surgery, can reduce the risk of these inherited forms of cancer.
Advances in imaging techniques are making it possible to detect cancer earlier, which can help eliminate tumors before they become life-threatening. New imaging techniques are also helping to guide surgery, so that tumors can be removed more precisely. Other leads are emerging from a better understanding of how tumors grow. Tumors need a plentiful blood supply, so they produce factors that induce the formation of blood vessels (a process called angiogenesis). New drugs, which have been designed to inhibit tumor angiogenesis, are showing promise in clinical trials.
It is estimated that 10 to15 percent of cancer worldwide is associated with viral infection. Liver cancer, which is associated with hepatitis, and cervical cancer, associated with human papilloma virus infection, are prominent examples. A vaccine against hepatitis B virus is proving to be effective in reducing the incidence of liver cancer. Rapid and specific diagnostic tests for the human papilloma virus are supplementing traditional Pap tests, helping to identify women at risk for cervical cancer.
One of the most intriguing discoveries of modern biology is that cell death is intimately involved with growth and development. For example, nerve cells are produced in excess, and some die in order for proper connections to be established in the nervous system. Cells contain a "suicide program" that is activated when the cells are damaged beyond repair. Intriguingly, cancer cells respond abnormally to death signals. Some of the genes involved in the suicide program are the same genes that are altered in cancer cells. A promising approach now being explored for treating cancer is to activate the suicide program of cancer cells without disturbing normal cells.
It seems reasonable to expect that the burden of cancer will be reduced substantially in the next ten years by new treatments. For some cancers, like liver cancer and chronic myelogenous leukemia mentioned, this is already happening. For other cancers, the means for prevention are at hand, but the application is problematical, as in the case of lung cancer caused by cigarette smoking. It is unlikely that most cancers will disappear in the near future; rather they will be diagnosed more precisely and treated more effectively, thereby increasing the number of people who can be cured.
Walter Eckhart is Professor of molecular and cell biology and Director of the cancer center at the Salk Institute for Biological Studies in San Diego, California.
copyright: Project Syndicate
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