New Study May Help Predict Chemotherapy Response

by VR Sreeraman on Sep 20 2008 11:47 AM

Scientists have found that cells from different people don't react the same way when exposed to the same DNA-damaging agent, something, which may help in understanding why chemotherapy works for some people and not for others.

During the study, the researchers from MIT's Centre for Environmental Health Sciences (CEHS) and the Departments of Biological Engineering and Biology, identified a group of 48 genes that can predict how susceptible an individual is to the toxic compound, known as MNNG.

MNNG, a DNA-damaging compound similar to toxic chemicals found in tobacco smoke and in common chemotherapy agents, usually kills cells by inducing irreparable DNA damage.

However, the researchers found a wide range of susceptibility among cells taken from healthy people.

"A cell line from one person would be killed dramatically, while that from another person was resistant to exposure," said Rebecca Fry, former MIT research scientist and lead author of the paper.

"It wasn't known that cell lines from different people could have such dramatic differences in responses," she added.

After measuring the expression of every gene in each cell line, the team could predict cell sensitivity to MNNG from the expression of just 48 specific genes, with 94 percent accuracy.

Toxics like MNNG create lesions in DNA, provoking the cell to defend itself with a variety of DNA-repair and other pathways. However, every individual expresses slight differences in the genes involved in those pathways.

"Even if everyone is exposed to exactly the same things, they would respond differently, because we're all genetically different," said Leona Samson, senior author of the paper, director of CEHS, and an American Cancer Society Research Professor.

The work appears online in Genes and Development.