Within the United States, 170,000 new cases of lung cancer are diagnosed per year and 60 percent of these patients will die within one year. New modes of diagnosis and targeted-therapy to address this critical health care problem are needed.
A potential paradigm for the diagnosis and treatment of lung cancer is to generate a panel of tumor-specific binding reagents. These reagents could be used to "classify" the tumor type and then to customize the treatment according to type by attaching the appropriate cell-targeting ligand to the anticancer drug. This would allow for a more refined molecular diagnosis of the tumor and creates "smart bullet" drugs that will be more effective and have fewer side effects. My group has isolated lung tumor targeting peptides and shown that these peptides can be utilized to deliver a chemotherapeutic in a cell-specific fashion in vitro. We have recently shown that these peptides can home to tumors in an animal. Our overall goal is to generate a panel of cell-specific molecules that could be used to classify tumor types and then be exploited for targeted delivery of therapeutics. Current efforts are to:
- Identify a panel of peptides that bind in a cell-specific manner to human lung cancer cells.
- Correlate the peptide binding profile to drug sensitivity and DNA microarray expression data. Binding to human tumor samples will be determined as well and correlated to patient prognosis.
- Identify peptides that can identify pre-malignant lung epithelial cells as a means to create diagnostic reagents for earlier detection of lung cancer lesions.
- Develop peptidic scaffolds that can be easily modified for the delivery of bioactive therapeutics and imaging agents.
- Use the peptide scaffolds to target tumors in animal models with the goal of moving to human clinical trials.
- Develop rapid high throughput diagnostic assays using the tumor specific peptides as probes.
- Use the identified targeting reagents to identify novel cancer-specific biomarkers.
More information can be found in the following publications:
- Elayadi, Anissa N.; Samli, Kausar N.; Prudkin, Ludmila; Liu, Ying-horng; Bian, Aihua; Xie, Xian-Jin; Wistuba, Ignacio I.; Roth, Jack A.; McGuire, Michael J.; Brown, Kathlynn C. (2007) “A peptide selected by biopanning identifies the integrin avß6 as a prognostic biomarker for non-small cell lung cancer” Cancer Res. 2007; 67:5889-5895.
- Oyama Tsukasa; Rombel, Irene T.; Samli, Kausar N.; Zhou Xin; Brown, Kathlynn C. (2006) “Isolation of multiple cell-binding ligands from different phage displayed-peptide libraries” Biosensors & Bioelectronics. 21, 1867-1875.
- Zhou, Xin; Chang, Ya-Ching; Oyama, Tsukasa; McGuire, Michael J.; Brown, Kathlynn C. (2004) “Cell-Specific Delivery of a Chemotherapeutic to Lung Cancer Cells” J. Am. Chem. Soc. 126, 15656-15657.
- Oyama, Tsukasa, Sykes, Kathryn F., Samli, Kausar, N., Minna, John D., Johnston, Stephen Albert, Brown, Kathlynn C. (2003) “Isolation of Lung Tumor Specific Peptides from a Random Library: Generation of Diagnostic and Cell-targeting Reagents” Cancer Lett. 202, 219-230.