The Future Outlook for Cancer
The Future Outlook for CancerTargeted Therapies
A Cure for Cancer?
Since President Richard Nixon signed the National Cancer Act in 1971, billions of dollars have been spent in the United States to fight the War on Cancer. Better ways of diagnosing and preventing cancer and of treating and caring for cancer patients have been discovered. Millions of cancer patients have survived much longer than would have been possible even a few decades ago. The war, however, is far from over, although tremendous progress has been made and a number of battles have been won. In this never-ending fight, older therapies are being refined and practically reinvented. In addition, outstanding scientists all over the world are exploring a number of exciting possibilities for improved diagnosis, treatment, and prevention of this dreaded disease.
For many years, surgery, chemotherapy, and radiation have been the standard methods used to treat cancer. Radiation works by causing DNA changes in cells. High doses effectively kill cancer cells, but even relatively low doses can cause changes in normal cells and may cause them to become cancerous. Before the dangers of radiation were fully understood, many early radiologists developed leukemia. Through research, radiation therapy is constantly improving. Now, concentrated beams of radiation are focused directly on the tumor site. This technique reduces the risk of harming adjacent tissues and also increases the dose that can safely be given.
Chemotherapy has also been a double-edged sword. It is usually given as a mix of toxic drugs that circulate through the body and kill rapidly dividing cells. Unfortunately, the drugs also interact with normal cells and can have moderate to severe side effects. In the past, doctors had no choice but to try to choose a dose that would kill the cancer cells before the toxic drugs killed the patient. New drugs are more effective in destroying cancer while doing less harm to healthy cells.
The advanced chemotherapy used today can still have disagreeable side effects. However, research is discovering ways to help patients tolerate them better, and modern medications make the problem of nausea and vomiting less severe. Antinausea, or antiemetic, drugs are given along with intravenous chemotherapy drugs, and the patient is instructed to take a second dose within an hour after the treatment ends.
Studies have shown that electro-acupuncture, in which pressure points are stimulated by a tiny electric current, may have real value in reducing the nausea that accompanies chemotherapy. Acupressure, where the patient applies pressure to acupuncture points, has also been found valuable in reducing nausea after chemotherapy.
The use of marijuana to relieve nausea, vomiting, and certain kinds of pain associated with cancer and chemotherapy is more controversial. Although some states have passed legislation allowing marijuana use for medical purposes, the Food and Drug Administration continues to insist there is no sound scientific basis for believing marijuana use has medical benefits. There are also studies that link a risk of head and neck cancer to habitual marijuana smoking. American Cancer Society expert Michael Thun agrees with this finding. He says, “Many of the same cancer causing substances in tobacco smoke are present in marijuana smoke. Marijuana cigarettes generally deposit more tar in the respiratory tract than tobacco cigarettes.”21 In 1985 the FDA approved dronabinol, a synthetic form of the active marijuana constituent delta-9-tetrahydrocannabinol (marketed as Marinol), as a prescription drug for use as an antiemetic. The pros and cons of the use of marijuana by cancer patients continue to be debated in Congress, in the news media, and on the Internet.
Many people, including scientists, consider targeted drugs to be the wave of the future. Gleevec was the first of these drugs approved by the Food and Drug Administration. It represents a new class of drugs and introduced a new way of thinking about cancer. Beginning in 1998, clinical trials showed dramatic responses to Gleevec in patients with advanced stages of cancer. In 2001 Gleevec was approved by the FDA for treatment of chronic myeloid leukemia, a cancer of white blood cells, and it was approved for the treatment of a form of stomach cancer called gastrointestinal stromal tumor (GIST) in 2002. Gleevec and other targeted drugs are designed to zero in on specific cancer-causing proteins. They destroy cancer cells but do not do serious damage to normal cells.
Tamoxifen is another targeted drug that has received a great deal of publicity. When it was first introduced, it was hailed by some doctors and patients as a miracle drug. Most breast cancers grow in response to estrogen. Tamoxifen works by blocking estrogen receptors on breast cancer cells. Studies showed that giving patients tamoxifen after breast cancer surgery reduced the chance that the cancer would return. Women were advised by their doctors to take tamoxifen for five years.
When it was found that the benefits of tamoxifen faded over time, allowing the cancer to start growing again, scientists at Duke University Medical Center proposed an explanation. The researchers suggested that tamoxifen initially works by preventing estrogen from binding to receptors in breast cells. The drug changes the shape of the receptors and prevents them from taking part in the process of cancer cell growth. Eventually, the report said, the cells adapt and recognize tamoxifen as an “estrogen,” allowing cell growth to proceed. Since the resistance to tamoxifen usually develops in two to five years, there seems to be little benefit in taking the drug for more than five years.
Almost immediately, another targeted drug came to the rescue. An article in the New England Journal of Medicine reported that “women who switched to the drug exemestane after 2 or 3 years of tamoxifen were less likely to see their cancer return than women who stayed on tamoxifen the full 5 years.”22 Other experts argue that it is too early to know whether exemestane and drugs like it are a better choice for some breast cancer survivors.
Obviously, the field of targeted drugs is still in its infancy, but the drugs' potential in fighting cancer is exciting. A step beyond simply developing and using targeted drugs is making them into designer drugs. Researchers now have the ability to profile cancer genes, examine them to see what makes them abnormal, and search for ways to disrupt their abnormal behavior. Doctors are able to personalize treatment by using specific drugs for people with a particular combination of defective genes. For example, Herceptin is used to treat certain types of breast cancer. About one-third of breast cancer patients have a gene called HER2, which causes cells to produce extra receptors, resulting in uncontrolled growth. Herceptin blocks these receptors, targeting only cells covered with huge numbers of the receptors. A test for the HER2 gene has been developed, which means doctors can prescribe Herceptin for exactly the breast cancer patients who can benefit from it.
Today, much cancer research is focused on the human immune system. Researchers are working to discover how the immune system functions to prevent cancer and how it can be used to cure cancer. Normally the immune system acts as the body's defense system, fighting cancer cells and keeping the body cancer-free by attacking the cells before they can grow and spread. When the immune system is weakened, it cannot do its job effectively. Immunotherapy (also known as biotherapy) takes advantage of the body's own ability to fight disease. It is aimed at strengthening the patient's immune system and helping it recognize cancer cells as undesirable aliens. Immunotherapy uses a number of different techniques.
Interferons are substances normally used by the body to fight viruses. They can be used to fight cancer by inhibiting the division of cancer cells so that they become sluggish and die. Artificially introduced interferons are powerful medicine. They stimulate antibody-producing B cells, killer T cells, and macrophages, which are white blood cells that gobble up foreign cells. As with many potent treatments, interferon treatments can have a number of unpleasant side effects. These may include temporary flulike symptoms and long-term problems such as chronic fatigue, memory loss, and depression.
Vaccines are another form of immunotherapy under intense investigation. Chemicals called antigens are usually found on the surface of cancer cells. Dead tumor cells that still have their surface antigens are used to make vaccines, but the antigens alone also may be used. The antigen vaccine is then injected into the body in an effort to prompt an immune response against the cancer.
Melanoma is one type of cancer that responds well to therapy that boosts immune responses against cancer. In Australia, which has the world's highest skin cancer rate, clinical trials with vaccines are being conducted, and the results are encouraging. Tim Stobo of Ballarat, Australia, enjoys golfing, surfing, and sailing. His regular exposure to the sun caused him to develop melanoma. After undergoing surgery and radiation, he joined the vaccine trials. When asked by a reporter how the trials were going, he said, “The people are very good. I ask semi-intelligent questions, they give responses I can understand, suggest reading I can do. They treat me like a researcher, in a way. And I have high hopes for the vaccine.”23
Much cancer research is being centered on antiangiogenesis. Angiogenesis, the formation of new blood vessels in the body, is a normal process. Blood vessels are needed to supply cells with the oxygen and nutrients they must have to live and grow. As a tumor gets bigger, its center cells get farther and farther from the blood vessels in the area where it is growing. Scientists now think a cancer tumor cannot grow much bigger than a pencil tip before it has to develop its own blood supply. Cancer cells send out signals to activate genes to produce proteins that stimulate the growth of capillaries. Once a tumor can stimulate the growth of new blood vessels, it can grow very quickly and stimulate the growth of hundreds of new capillaries to bring it nutrients and oxygen.
Experts now believe angiogenesis may also explain why a secondary cancer can appear years after the primary cancer has been discovered and treated. The tiny secondary tumor may have lain dormant without a supply of oxygen or nutrients. Then, through mutation, the cells may suddenly be able to trigger capillary growth, and the cancer comes to life and begins growing rapidly.
By inhibiting tumor angiogenesis, a basic requirement for malignant growth is blocked. The challenge is to find drugs that will interfere with the ability of a cancerous tumor to stimulate blood vessel growth. A number of inhibitor drugs are available, and scientists are working to find the most effective ways to use them to starve cancer cells without causing undesirable side effects for the patient. Examples of drugs under study for the purpose of antiangiogenesis are interferon alpha, avastin, and thalidomide.
In the early 1960s, thalidomide acquired a bad reputation. For years European doctors had prescribed it as a mild sleep aid and antinausea remedy. After thousands of women who had taken the drug to ease their morning sickness gave birth to babies with tiny flippers instead of arms and legs, it was withdrawn from the market. Recently it has made a comeback as an angiogenesis inhibitor. Researchers have found that the drug, which stunted limb develoment in embryos by blocking the formation of blood vessels, could also stunt the growth of tumors. In 2006 thalidomide received FDA approval, and the villain returned as a hero.
There are numerous cancer research organizations, large and small, in many countries worldwide. Some are connected with hospitals and other treatment centers and some operate independently. The National Institutes of Health is an important United States agency devoted to medical research. It operates under the Department of Health and Human Services and consists of twenty-seven separate institutes and centers. Among them is the National Cancer Institute. The mission of the NCI is
to lead a national effort to reduce the burden of cancer morbidity and mortality and ultimately to prevent the disease. Through basic and clinical biomedical research and training, NCI conducts and supports programs to understand the causes of cancer; prevent, detect, diagnose, treat, and control cancer; and disseminate information to the practitioner, patient, and public.
The NCI's Cancer Information Service is a national information and education network for patients, the public, and health professionals. From regional offices covering the entire United States, trained staff provide the latest cancer information through a toll-free telephone service.
Quoted in “Definition of National Cancer Institute (NCI)” www.medterms.com/script/main/art.asp?articlekey=6780.
Scientists are just beginning to tap into genetics and the profiling of cancer genes. Since it is a change in a person's DNA that causes cancer, some think that a cure for cancer may lie in the human genetic code. Gabriel N. Hortobagyi, director of the multidisciplinary breast cancer research program at the University of Texas M.D. Anderson Cancer Center in Houston, says, “For the past 50 years oncologists tested hundreds of thousands of compounds on cancer cells to see if they would slow the growth or destroy them. It was very inefficient. Now we can profile cancer genes, understand what makes them abnormal, then look for very specific ways to disrupt those processes. This is a revolution. Instead of developing 50 drugs over 50 years, we're developing 10 or 20 drugs every year.”24
In April 2008 researchers announced that they had identified genetic quirks that increase the risk of lung cancer in smokers and former smokers. Three international teams each pinpointed the same genetic link to cancer risk. Their findings on genetic links are a major breakthrough that will help researchers identify people who are at high risk for non-small cell lung cancer, the most common form of the disease. Identifying those at high risk is important, because there are usually no symptoms until the cancer is in an advanced stage.
In the future, doctors may be able to replace defective genes before a person develops cancer. In the meantime, the search goes on for substances that can cause changes in cells that may lead to cancer. The cancer research branch of the World Health Organization tests and evaluates agents that have cancer-causing potential. Out of about nine hundred substances they have tested, about ninety are classified as “carcinogenic to humans.”25 The National Toxicology Program in the United States releases a report on carcinogens every two years. The report divides the tested agents into those known to be human carcinogens and those that are probably carcinogenic to humans.
Debates arise almost every day concerning the possible danger of suspected cancer-causing agents. Recent stories about nanotubes claim that they are as dangerous as asbestos. The federal government has heavily funded the development of nanotechnology, which involves the use of particles a few billionths of a meter in diameter. Carbon nanotubes have become the basic building blocks utilized in the making of some electronic components, appliances, toys, and dozens of other products. Preliminary evidence of their cancer-causing potential in tests with mice is strong enough to cause concern for workers in nanotech factories. In an article in the journal Nature Nanotechnology, researcher Anthony Seaton said, “In a sense we are forewarned and forearmed now with respect to nanotubes. We know that some of them probably have the potential to cause mesothelioma [a fatal form of cancer]. So those sorts of materials need to be handled very carefully.”26
When traditional ways of treating cancer through surgery, chemotherapy, and radiation do not seem to be working or become difficult to take, some patients turn to alternative treatments. These may include radical diets, herbal remedies, yoga, acupuncture, and homeopathy. (Homeopathy is a method of treating a disease by giving patients a minute amount of a substance that causes symptoms similar to those resulting from the disease.)
In May 2008, medical journalist Susan Aldridge reported, “A survey within Europe reveals that one cancer patient in three is using some kind of complementary or alternative medicine. The number in the United States is even higher, and users tend to be younger, [to be] female and to have cancer of the bone, brain, pancreas or liver—in other words, those cancers with a poorer prognosis.”27
The National Cancer Institute reviews and tests alternative treatments to determine whether they are effective. One concern is that the alternative treatments may have harmful side effects that outweigh any possible benefit. Other alternative treatments may be safe but have little or no benefit. According to cancer doctors, the gravest danger is that patients using alternative treatments may give up standard treatments that might be more effective in fighting the disease. The medical community currently does not accept many alternative approaches, despite the fact that there are cancer survivors who believe that alternative treatments have saved their lives. The research and the debates over alternative treatments continue. One possible result is that some alternative treatments may be combined with traditional treatments to make life easier for the patient.
Soon after the United States government declared the War on Cancer, there was much talk of discovering a “magic bullet” that would seek out and destroy cancer cells throughout the body. That dream has still not become reality. There are so many differences among the several hundred diseases that are called cancer, it seems unlikely that any one treatment will be useful in all cases. However, scientists have acquired a tremendous amount of knowledge about how each cancer occurs and about the possibilities of curing it. As Paraic A. Kenny says in Stages of Cancer Development, “Although we may never find that so-called magic bullet, we will soon have an array of mini-bullets that we can mix-and-match depending on the characteristics of the individual tumor. It is hoped that these cocktails will prove much more effective than the ‘cut it out, burn it out, and poison it’ approach of surgery, radiation therapy, and chemotherapy.”28
While researchers work around the clock to develop successful mini-bullets to seek and destroy cancers, there are a number of ways people can help protect themselves. People can avoid known risk factors as much as possible. They can stay healthy by exercising and maintaining a healthy weight. They can reduce fat intake to less than 25 percent of total daily calories and eat vegetables, fruit, and whole grains every day.
Stem cells may be a key to unlocking some of the mysteries still lying behind the complicated disease known as cancer. There are two basic types of stem cells. Embryonic stem cells usually come from fertilized eggs that have been discarded after a fertility treatment. When an egg is fertilized, it begins to divide. After about five days, the egg is a collection of about 150 cells known as a blastocyst. The inner cells of the blastocyst are stem cells that can grow into any type of cell in the body. Research on the uses of human embryonic stem cells has been restricted by legislation.
Scientists have used adult stem cells for therapeutic purposes for more than three decades. They are found in many places in the body, but they are not as versatile as embryonic stem cells. The adult stem cells can only form a closely related family of cells. One advantage of adult stem cells is that they can come from within an individual's own body, making it less likely they will be rejected by the patient's immune system.
One example of how these stem cells are being used is in bone marrow mini-transplants. The donated cells multiply and gradually take over the bone marrow. So far stem cell transplants, or grafts, have worked best in treating patients with chronic myeloid leukemia.
People can also stay informed about the progress being made against this disease. Everyone can learn about the local organizations in their areas that offer support and resources to cancer victims. And perhaps some can find a way to join the fight to end the long struggle against this killer.