A new computational method that can be used to determine how gene networks are rewired after normal breast cells turn malignant has been developed by researchers at Carnegie Mellon University who made use of high-throughput data generated by breast cancer biologists at Lawrence Berkeley National Laboratory.
This method for analyzing how genes interact with each other in laboratory-grown cells is described in a report published today by the online journal PLOS Computational Biology. The method could provide new insights into cancer and identify the most promising molecular targets for drug therapy. In their study, for instance, the researchers were able to show how changes in these gene networks led breast cancer cells to develop resistance to several different agents being evaluated as drugs for targeted therapy.
"With our system, pharmaceutical developers wouldn't need to go to expensive clinical trials to discover that a drug isn't going to work," said Wei Wu, associate research professor in CMU's Lane Center for Computational Biology. "It could save them a tremendous amount of money and a tremendous amount of time." The approach also might be used to detect differences in gene regulation between individuals, helping physicians select which treatment will be most effective for each patient, she added. Wu and Eric P. Xing, associate professor of machine learning, worked with Mina Bissell, a renowned breast cancer researcher at the Berkeley Lab, to investigate whether distinctly different gene regulatory networks could be identified within cells as normal cells become malignant and as the malignant cells respond to various drug treatments. The researchers studied these breast cancer cells using a 3D cell culturing technique developed by Bissell's laboratory. These networks can be inferred based on microarrays, which measure the expression levels of tens of thousands of genes in a cell. But the number of microarrays that investigators can afford to run for each cell state — normal cells, malignant cells and malignant cells that have reverted to normal-looking cells that also are organized normally — is limited.