Decoding DNA for better diagnosis
and drug development
by Susan Craig
News reports announce new genes associated with specific types of cancer almost daily. But cancer has many guises, making diagnoses elusive and complicating the development of new or improved drugs.
Utilizing functional genomics, Children's investigators are hopeful that as they learn more about the genes involved in different types of cancer, diagnosis and treatment methods will improve. These researchers, in collaboration with scientists at the Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research in Cambridge, analyzed the genes of 60 different tumor lines provided by the National Cancer Institute. Their goal is to match gene expression data from each cancer with pharmacological data to determine which anti-cancer drugs are most successful in fighting individual cancers.
Using a technique called Relevance Networks, a computerized method of clustering gene groups, the researchers have discovered relationships among the data sets. The most notable finding was a link between the gene LCP1 (lymphocyte cytosolic protein-1) and a chemical found commonly in a type of anti-cancer drugs. They found that the lower the level of LCP1 in any of the cancers, the more effective the drug was in halting cancer growth.
"We're learning about new links between drugs and disease that will very likely lead to better treatments for patients," says Atul Butte, MD, fellow in Pediatric Endocrinology and Informatics and first author on the paper detailing these findings in the Proceedings of the National Academy of Sciences (October 2000).
Marsha Moses, PhD, a principal investigator in the Surgical Research Laboratories at Children's headed by Judah Folkman, MD, is also working on the sequencing of cancer genes. Folkman's belief that tumors cannot survive without the process of angiogenesis, or the recruitment of blood vessels to feed them, has been a guiding principle of researchers in Children's Surgical Research Laboratories for more than 30 years. Moses and her colleagues have developed a novel in vivo model to study the switch to angiogenesis during tumor growth. They have isolated mRNA (the copy of the DNA that controls protein function) from a series of tumors that accurately represents the stages in this progression and have analyzed it using gene chip technology. Moses' lab is currently analyzing the sets of genes most strongly affected during this angiogenic switch. "These data may provide us with strong therapeutic candidates and clinical intervention sites that will lead to the earliest detection and suppression of tumor progression," says Moses.
