Recombinant Peptides as Biomarkers for Tumor Response to Molecular Targeted Therapy

Purpose: Phage display technology can be used to identify peptide sequences that bind rapidly and specifically to tumors responding to sunitinib therapy. These pepticles may help to address problems with current methods of assessing tumor response to therapy that can be slow and have limited usage. Experimental Design: The peptide of interest was isolated after four rounds of biopanning in MDA-MB-231 and MCF-7 xenografted tumors. The binding location of the peptide was investigated with immunohistochemistry. Its in vivo ability to bind to breast tumors responding to therapy was determined by treating nude mice, xenografted with various tumor cell lines, with sunitinib and using near IR imaging to assess the ability of the peptide conjugated to Alexafluor-750 to bind tumors. Results: EGEVGLG was the dominant sequence isolated from biopanning. This peptide showed increased binding relative to control groups in two cancer cell lines (MDA-MB-435 and MCF-7 human breast) responding to sunitinib treatment, whereas no elevated binding occurred in vitro when samples were incubated with tumor cells that are unresponsive to sunitinib treatment (1316 melanoma and BxPC3 pancreatic). Mice xenografted with tumors that are responsive to sunitinib therapy showed increased peptide binding when compared with untreated control. Mice bearing tumors unresponsive to sunitinib therapy showed no increased peptide binding between treated and untreated groups. Conclusion: The use of recombinant peptides to assess the pharmacodynamic response of cancer holds promise in minimizing the duration of ineffective treatment regimens in patients, potentially providing a more rapid and less invasive assessment of cancer response to systemic therapy. (Clin Cancer Res 2009;15(20):6421-9)