By Allison Proffitt
August 5, 2010 | Yesterday, Merck scientists published new research showing that biomarkers for the PI3 signaling pathway can predict the sensitivity of cancer cells to AKT-inhibiting drugs. The research was published in the August 4 issue of Science Translational Medicine and included authors from Merck, the Fred Hutchinson Cancer Research Center in Seattle, Biogen Idec, and Daiichi Sankyo.
The research features phosphoproteomics, a technology that measures the addition of phosphate groups to serine or threonine residues on cellular proteins to identify drug-specific biomarkers for PI3-kinase pathway inhibitors. “There is published evidence of PI3K-signaling disregulation in many human cancers including ovarian, breast and lung cancer,” author Ron Hendrickson of Merck Sharp & Dohme told Bio-IT World over email.
Researchers looked at 375 phosphorylation sites in the PI3-kinase pathway, and used three pathway inhibitors to identify drug-regulated phosphorylation events. Each of the three test drugs modulated a specific array of phosphopeptides, with some overlap. The hope, Hendrickson said, is that “by measuring biomarkers in tumor tissue before treatment, clinicians can directly test whether the cancer-causing mechanisms that a drug specifically targets are active in the patient’s tumor.”
Merck researchers focused on three early pipeline drug candidates that inhibit AKT, an enzyme that spurs cell growth, said Hendrickson. “Merck may seek to explore the full impact that this technology could have on our oncology pipeline of kinase inhibitors as well as our broader pipeline but it is still early days.”
Most tumor characterization looks at genetic mutations causing cancer, but this approach provides only vague information about the molecular causes of tumor growth. Phosphoproteomics, however, reveals activated pathways in tumors, providing a more precise way to directly tell whether or not a certain drug will work for a patient.
“These results point to a way, after further development of more biomarkers, to routinely characterize the activated pathways in patients' cancers,” said Hendrickson. “A characterized tumor can then be treated with the appropriate pathway-specific drugs, optimizing the chances of eradicating the tumor.”