Despite this success, many challenges remain and the first is obvious -- the cure rate isn't 100%. And, until it is we must work toward this goal. A second goal is to develop treatments with fewer side effects. To achieve these goals we must discover the root causes of childhood leukemia. In this regard, the future is bright. We are beginning to unravel the events that cause a single cell to become cancerous. These results can be attributed to significant advances in basic research, especially in the area of genetics. When we talk about cancer genetics we mean two different things. The first, which is readily understood, means inheriting a high risk of cancer from one's parents. This is only a small minority of all cancer cases and is very rarely the cause of childhood cancer. The second meaning of genetic is that the cancer cell has acquired damage to its genes, while the rest of the body's cells have a perfectly normal genetic make-up.
In the case of ALL, we know that a single normal cell, destined to become a normal white blood cell called a lymphocyte, develops a mistake in the genetic code. In the case of leukemia, this is a swap of genetic material between two chromosomes and is called a translocation. These translocations occur in genes that control growth under normal circumstances. When such growth-promoting genes are damaged, the cell will continue to grow even when the body is trying to send a message to tell it to stop growing. Through the development of powerful techniques we now know the location of many of these defects and researchers at many centers are working to unravel the complexity of the cancer cell to understand specifically changes that allows the cancer to grow.
Perhaps the most difficult questions for a physician to answer are, "Doctor, why did my child get leukemia? And, was there anything I could have done to prevent it"? The answer to the second is a resounding "no." The answer to "why" is that we don't yet know the fundamental cause of ALL.
When clusters, or dramatic increases in cancer cases in small geographic areas, occur, we always revisit the issue of whether a cancer-causing agent from the environment or an infection resulted in the increased number of cases. Unfortunately, this approach has not identified any causes for ALL. But it is possible that we are missing subtle relationships if an environmental or infectious cause is present but only affects individuals with a certain genetic makeup and not all members of the population.
The recent sequencing of the human genome provides us with unprecedented opportunities to understand cancer and to use that knowledge to develop new treatment and prevention. The major focus of the Huntsman Cancer Institute (HCI) is to understand this genetic blueprint of cancer. Using a new technology called "DNA chips" investigators in our childhood cancer program have uncovered genetic pathways that are active in cancer cells but not normal blood cells. Using this information it may be possible to develop drugs that could interfere with these active pathways. Since these changes are limited to the cancer, new drugs targeted to these pathways might avoid the side effects seen with conventional drugs.
We also now know that certain pathways are unique to groups of patients that have a greater risk of relapse after treatment. It may be possible to use the genetic "fingerprint" of the leukemia someday to "tailor" therapy so that patients with a high likelihood of cure can be treated without exposing them to unnecessary more toxic therapy, while patients with high risk disease can be more effectively treated before the leukemia comes back. This approach is still experimental and leukemia samples from children treated at children's hospitals throughout the United States will be sent to us to test further this genetic approach to classifying leukemia. We believe that the same approach could be applied to studies of clusters of ALL to try to understand why they occur. For example, is there a specific genetic pathway damaged in children from Fallon who have ALL. If so, this would suggest that an infection or environmental agent initiated a common form of damage.
The Children's Oncology Group, a consortium of all major children's hospitals in North America, is embarking on a massive effort to identify a subset of patients who might be especially vulnerable to environmental risks because of inherent susceptibility to damage from chemicals. This effort will use the approach I've described and will be led by Dr. Bill Carroll, the deputy director of the Huntsman Cancer Institute.
Although these projects are just underway, progress is being achieved at a remarkable rate. By combining sophisticated genetic analysis of patients and their tumors with the best treatments available, we hope to reach that goal of uniform cancer cure and ultimately, prevention.