Future Trends In Cancer Treatment
John W. Anagnost, M.D.
Cancer continues to be a frightening thought for most Americans. But research has led to dramatic improvements in cancer survival over the last 25 years. In the past survival in childhood cancers was measured in weeks to months, but now more than 70% of children with cancer can be cured. Death rates from Hodgkins disease and testicular cancer have also fallen dramatically, moving from incurable to mostly curable. Finally death rates from cancers of the colon and rectum, breast cancer, prostate cancer and lung cancer (in men) have dropped steadily since 1991. The overall cancer death rate in the US declined 2.6% between 1991 and 1995. It has fallen 4.3% for men and 1.1% for women. Unfortunately, the decline in women was less because of the epidemic of lung cancer in females. The most important advance in the last 25 years has been our understanding of the fundamental biology of cancer. All cancers arise from changes in the DNA of one of the trillions of cells in the human body. DNA or genes are the instructions that guide the behavior of all cells. Scientist now know that cancer occurs when there is an abnormality in the normal function of our genes. When cells become cancerous it is because there is a problem in the genes that control cell growth and division.
The Human Genome Project will soon tell us about the 30,000 to 35,000 genes that are in the human body. One result of this project will be that we will learn what normally regulates cell growth. We will then learn what errors occur in these genes to cause cancer. Though some of these errors are inherited most are acquired during years of living. Sunlight, cigarette smoke, environmental toxins, and the normal aging process cause these errors to occur.
New treatment will exploit more efficient and elegant ways to treat these abnormal cells. Up to now we have used chemotherapy, surgery or radiation therapy to treat cancer. Chemotherapy is the use of chemicals that are injected into the body to kill cancer cells. Chemotherapy is toxic to both cancerous and normal cells. However, because cancer cells divide more rapidly than normal cells they are more affected by chemotherapy. In this way chemotherapy will kill cancer cells while leaving normal cells affected but alive. The most rapidly dividing cells of the body include blood cells, hair cells, and cells that line the gastrointestinal tract. These are the cells that can be significantly affected by chemotherapy causing the common side effect seen with chemotherapy - nausea, vomiting, hair loss and low blood counts. Radiation therapy is the use of radiation directed at specific parts of the body (brain, breast, lung, prostate, etc.). Even though it does not affect the entire body, it can still cause serious side effects to the normal tissues in the vicinity of the cancer being treated. Future treatments (by being more specific) will cause much fewer side effects.
Rituxan and Herceptin are two such new weapons. They are both examples of the new technology that uses the body’s immune system to fight cancer. Monoclonal antibodies are proteins normally made by the body to fight infection. Pharmaceutical companies have made monoclonal antibodies against specific cancers. Once a monoclonal antibody attacks a cancer cell it also summons a person’s immune system to help destroy that cell. Rituxan is a new treatment for non-Hodgkins lymphoma which attacks the CD-20 antigen. This is a protein that is found on many (but not all) lymphoma cells. Studies have now shown a significant improvement in the survival in some patients with lymphoma who are treated with Rituxan while at the same time they have much fewer side effects. Herceptin is another antibody now available that is being used in the treatment of breast cancer. It targets another specific protein which is found only in breast cancer (but not all breast cancers). That protein is the Her-2/neu protein. Finally, several pharmaceutical companies are investigating a growth protein made by the RAS gene. In almost 30% of cancers the RAS gene is stuck in the “on position” causing the cell to continuously divide. It plays a roll in 90% of pancreatic cancers, 50% of colon cancers and 25% of lungs cancers. By blocking the RAS protein (with a monoclonal antibody) you can stop these cancers from growing any further. In each of these situations only “marked” cells are destroyed by the immune system and we have a very specific treatment without a lot of damage to other cells in the body.
As we learn more about cancer, we realize that one essential property is being able to grow new blood vessels. All cancers need blood to grow and spread, and they cannot grow beyond the size of a pinhead without making new blood vessels to feed them. One of the most exciting new areas is the development of medicines to block the formation of new blood vessels (angiogenesis inhibitors). By blocking the development of new blood vessels researcher hope to cut off the tumor’s supply of oxygen and nutrients and starve the cancer. There are nearly two dozen angiogenesis inhibitors now being studied for use in humans (thalidomide being the most well known). Last year Harvard researchers made headlines by successfully shrinking tumors in mice by this method. Unfortunately it will take several more years before we know how helpful angiostatin, endostatin or anti-VEGF (vascular endothelial growth factor) will be.
Another way where understanding the genome will help, is with cancer screening. We have just recently learned about two new genes that promote breast cancer (but in a very small and specific population). This is the BRCA-1 and BRCA-2 genes and we can now screen high risk populations (certain Ashkenazi Jewish females) for this gene. Most experts feel the Human Genome Project will lead to the discovery of other such genes. Some day we may be able to predict what cancers a particular person may develop and even prevent these cancers from ever starting to develop!