Research Mechanics: Putting the Brakes on Cancer
Cancers are caused by an accumulation of mutations that alter the activity of genes involved in controlling cell birth, growth, and death. Some of these errors are inherited. Most, however, occur after birth, triggered by cancer-causing agents in the environment or by mistakes that happen when cells divide. If the growth of cancer can be likened to a car speeding out of control, the mutations that cause the disease are the functional equivalent of cutting the brakes, gluing down the accelerator, or hiring an inept mechanic—or doing all three at once. Dr. Vogelstein explains that although there are numerous kinds of cancer, all stem from alterations that allow cell division to outstrip cell demise.
Chaos to Cure: Bringing Basic Research to Patients
The identification of hundreds of genes involved in the formation and spread of cancer is leading to promising new methods for diagnosis, prevention, and treatment. In the case of colon cancer, researchers are developing genetic tests for detecting the cancer-causing mutations. Researchers are also investigating anticancer therapies that take advantage of the molecular differences between cancer cells and the normal cells surrounding them. Gleevec, for example, is a compound designed to disable a protein that spurs the growth of certain types of leukemia. In Dr. Vogelstein's lab, scientists are deploying specialized microbes to penetrate tumors, proliferate rapidly, and kill the cancer cells.
A Healthy Nervous System: A Delicate Balance
Mutations in key genes can lay waste to the nervous system. Spinocerebellar ataxia type 1 (SCA1), for example, can start with a stagger at age 30 or 40. Patients eventually experience severe muscle deterioration, rendering them unable to talk, swallow, or even breathe. By studying large families predisposed to developing SCA1, Dr. Zoghbi and her colleagues identified the responsible altered gene. The culprit is a sort of genetic stutter that increases the size of the SCA1 gene. As a result, the product of the mutant gene—a protein called ataxin-1—forms large, sticky clumps that disable the neurons involved in controlling movement. Dr. Zoghbi is now searching for compounds that will clear ataxin-1 tangles.
The Strength of Families: Solving Rett Syndrome
Girls with Rett syndrome develop normally for about 18 months and then begin to regress. Eventually, they have difficulty walking, speaking, and even using their hands. With the help of affected girls and their families, Dr. Zoghbi and her collaborators searched for the gene responsible for this neurological disorder. After 16 years, they found the gene, called MECP2, on the X chromosome. It encodes a protein essential to the normal functioning of nerve cells in the brain. Mutations in the gene disrupt the activity of neurons early in life, when they are forming critical connections. Dr. Zoghbi discusses how identification of this gene should lead to better methods for diagnosing and treating Rett syndrome.
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