Whitehead Institute scientists report that certain molecules present in high concentrations on the surfaces of many cancer cells could be exploited to funnel lethal toxic molecules into the malignant cells. In such an approach, the overexpression of specific transporters could be exploited to deliver toxic substances into cancer cells.
Although this finding emerges from the study of a single toxic molecule and the protein that it transports, Whitehead Member David Sabatini says this phenomenon could be leveraged more broadly.
"Our work suggests a different strategy for cancer therapy that takes advantage of the capacity of a cancer cell to take up something toxic that a normal cell does not," says Sabatini, who is also a professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) investigator. "As a result, that toxic molecule would kill the cancer cell. By identifying transporters on the surface of cancer cells, you might be able to find a molecule that a specific transporter would carry into the cell, and that molecule would be toxic to that cell. You really could have something that's much more selective to cancer cells."
The Sabatini lab's research is published online today in the journal Nature Genetics.
Kivanc Birsoy, a postdoctoral researcher in Sabatini's lab and first author of the Nature Genetics paper, used a special line of haploid cells developed by former Whitehead Fellow Thijn Brummelkamp to screen for genes that assist cellular entry of 3-bromopyruvate's (3-BrPA), a potential cancer drug in clinical development. 3-BrPA is thought to work by inhibiting glycolysis, a cellular process that releases energy by splitting glucose molecules. Because many cancer cells are heavily dependent on the upregulation of glycolysis, drugs that interrupt this pathway may be effective in targeting these glycolytic cancer cells.