ATM and the Future of Cancer Treatment and Prevention



Dr. Michael Kastan, chair of hematology/oncology, announced in January 2003 that a discovery made in his laboratory at St. Jude could lead to better ways to treat cancer and new ways to prevent cancer. It could also lead to the development of sensitive methods to determine whether people have been exposed to radiation or environmental toxins. Dr. Kastan’s finding is important because exposure to radiation and many other environmental toxins causes breaks in the DNA of cells. Cells must respond to these breaks by triggering a series of biochemical reactions that lead to repair of the damage. Otherwise, the damage may lead to genetic mutations that cause diseases, such as cancer. Dr. Kastan made a key discovery related to how the cell responds to such damage within seconds after it occurs.

Fellow St. Jude researcher and colleague Dr. Christopher Bakkenist discovered a novel biochemical process that plays a critical role in helping cells in the body respond to DNA damage, such as that caused by exposure to radiation, environmental toxins, or free radicals. This critical process is a chemical modification of an enzyme called ATM (Ataxia-Telangiectasia Mutated). The modification activates ATM and allows this enzyme to initiate a series of events that ultimately halts the growth of a damaged cell and helps the cell survive.

The St. Jude researchers found that ATM is activated by a signal from damaged DNA only seconds after the damage occurs. The activated ATM, in turn, activates other proteins, setting off a cascade of biochemical reactions that amplifies the initial ATM response.

The excitement surrounding this finding is based on ATM’s central role in a cell’s response to irradiation. Blocking the activation or activity of ATM might make virtually any type of tumor much more sensitive to radiation therapy. So the discovery of these new molecular mechanisms should help Kastan develop a way to block ATM activity, which would improve the patient outcomes of radiation therapy for virtually all tumors.

The St. Jude researchers also developed an antibody that specifically recognizes activated ATM, and thus identifies only those ATM molecules that are responding to DNA damage. This antibody could become the basis of a very sensitive test to determine if cells in a person have been exposed to an agent or toxin that damages DNA. Such an assay has many potential applications, including the assessment of exposure to dangerous agents in the environment.

 


 


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