Oncologists and cancer patients could improve the results of drug therapies by making real-time decisions about treatment options using an innovation developed by a researcher in Purdue University’s College of Pharmacy.Laurie Parker, assistant professor of medicinal chemistry and molecular pharmacology, is developing a method to detect if cancer-inhibiting drugs are entirely blocking the activity of enzymes, called kinases, in tumor cells. Several kinases are linked to cancer development. If a drug therapy only partially blocks kinase activity, the cells that survive could become a stronger tumor and develop a resistance to the drug.
“Currently, the only way doctors and patients learn if kinase activity is being blocked is by watching and waiting. Sometimes it takes months or years before signs of resistance are visible as the tumor regrows,” Parker said. “By the time it is detected, the relapsed tumor can’t be treated with that drug anymore.”
Parker and her graduate students created a method that works like a search engine by taking a lot of information about what a particular kinase looks for in a substrate, or the protein it acts upon. The technology narrows the information to a shortlist of traits, including being acted upon by only one kinase and providing the signal that the test seeks.
“The test uses the ‘artificial’ substrate we develop as a decoy, introducing it into the tumor cell and tricking the kinase into acting on it. If the kinase’s function is effectively blocked, we don’t see this action. Cancer drug dosages could be monitored and adjusted based on the test,” she said. “It also provides a general process to design a version of this pharmacodynamics test for virtually any kinase. It can be used for different cancer types and treatment strategies.”
Parker’s work also could benefit pharmaceutical companies as they complete initial drug screening and clinical trials.
“The companies could ensure they were developing the best possible application for their newest drugs and receive information about why some patients in a trial might not have success with the drugs,” she said. “As drugs become available in less expensive generic forms over the next few years, patients and insurance companies would have information about whether a generic treatment works as well as a non-generic, or if a non-generic drug is required for a given individual.”
Parker’s work has been sponsored by the National Institutes of Health, the U.S. Department of Defense, the Purdue Center for Cancer Research, the Cancer Prevention Internship Program, the Walther Foundation and the Indiana Clinical and Translational Sciences Institute.
“We are working with Dr. Hamid Sayar at the Indiana University Simon Cancer Center and its Hematological Malignancies Tissue Bank to test our methods,” she said. “We are testing blood samples from leukemia patients taken before and after their treatment begins.”
Date: February 18, 2014
Source: Purdue University
