Peptide Binding May ID Early Responders to TKI Plus RT

LOS ANGELES—Vanderbilt University researchers have developed a noninvasive technique for monitoring the response to treatment with tyrosine kinase inhibitors (TKIs) and radiation therapy (RT), they reported at the 2007 American Association for Cancer Research annual meeting (abstract 4657).

"We need a rapid and noninvasive system to inform us right away whether the tumor is responding to treatment," co-investigator Roberto Diaz, MD, PhD, a resident in radiation oncology at the Vanderbilt-Ingram Cancer Center, said at an AACR press conference. Principal investigator is Dennis Hallahan, MD, professor and chairman of the Department of Radiation Oncology at Vanderbilt University Medical Center.

The researchers used a phage-displayed peptide library (named for the bacteriophage viruses used to capture protein fragments) to screen lung and brain tumor xenografts being treated with radiation to determine which peptides were able to recognize specifically those tumors that were responding to the treatment. With this library, they could select peptides that bind to tumors being affected by combined treatment with TKIs and radiation and not to tumors that do not respond to therapy. Ultimately they isolated 44 peptides that appeared to serve as biomarkers for response.

To validate the biomarkers, they injected these peptides into mice being treated for various solid tumors. Using near-infrared resonance imaging, they observed within just 48 hours that the peptides bound most robustly to tumors responding to treatment. This finding was confirmed with immunohistochemical staining. This was consistent across several tumor types, including glioma and lung, breast, prostate, and colon cancer.

"Our study provides us with a starting point for understanding how tumors physiologically respond to therapy and a noninvasive technique for monitoring that response," Dr. Diaz said. His team hopes to employ this technology in phase I trials beginning in 2008.