In proteomic mass spectrometry the researchers first break up cancer cells, purify their proteins, and cut them up. They then further purify stretches of protein characteristic of active tyrosine kinases. This mixture is put into the mass spectrometry machine, which sequences the proteins. With this information, researchers know which proteins are abnormally active and why – because of a mutation, for example – and can search for a drug that acts against them.
Tyner hopes their work can be translated into clinical tests for determining the molecular cause of a patient’s tumor. Protein mass spectrometry profiles of cells from a tumor biopsy could identify which protein is running amok and what drug would work best on it. “It’s very attractive, the idea of looking at signaling in tumors and from that uncovering [genetic] profiles,” says Cobbold.
Forest White, assistant professor of biological engineering at MIT, who uses mass spectrometry to study cell-signaling networks, is more cautious about direct clinical applications for the mass spectrometry technology: “It’s hard to imagine a mass spec in every hospital,” he says, because the results require expert interpretation. White points out that even scientists with advanced biological research labs have trouble reading mass spectrometry results. Instead, he suggests that the real value of using mass spectrometry to analyze a cell’s protein content lies in the possibility for a dynamic understanding of how cancer cells behave in different stages of the disease. In his lab, for example, White exposes cancer cells to a growth factor and uses mass spectrometry to quantify how the factor affects the activity of the cells’ tyrosine kinases.
In fact, Polakiewicz of Cell Signaling Technology says drug companies have expressed interest in the technology for just this purpose. Mass spectrometry might be used during cancer drug development to assay a compound’s effects on cancer cells’ signaling proteins.