New research from MIT may allow scientists to develop a test that can predict the severity of side effects of some common chemotherapy agents in individual patients, allowing doctors to tailor treatments to minimize the damage.
The study focused on powerful cancer drugs known as alkylating agents, which damage DNA by attaching molecules containing carbon atoms to it. Found in tobacco smoke and in byproducts of fuel combustion, these compounds can actually cause cancer. However, because they can kill tumor cells, very reactive alkylating agents are also used to treat cancer.
The new paper, which appears in the April 4 issue of the journal PLoS Genetics, reveals that the amount of cellular damage that alkylating agents produce in healthy tissues can depend on how much of a certain DNA-repair enzyme is present in those cells. Levels of this enzyme, known as Aag, vary widely among different tissues within an individual, and among different individuals.
Leona Samson, a member of MIT’s Center for Environmental Health Sciences and the David H. Koch Institute for Integrative Cancer Research, is the senior author of the paper. She has previously shown that when alkylating agents damage DNA, the Aag enzyme is called into action as part of a DNA-repair process known as base excision repair. Aag cuts out the DNA base that is damaged, and other enzymes cleave the DNA sugar-phosphate backbone, trim the DNA ends and then fill in the empty spot with new DNA.
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