Identification of pancreatic cancer-specific cell-surface markers for development of targeting ligands.
Pancreatic cancer is generally detected at later stages with a poor prognosis and a high-mortality rate. Development of theranostic imaging agents that noninvasively target pancreatic cancer by gene expression and deliver therapies directly to malignant cells could greatly improve therapeutic outcomes. Small-peptide ligands that bind cell-surface proteins and are conjugated to imaging moieties have demonstrated efficacy in cancer imaging. Identification of cancer-specific targets is a major bottleneck in the development of such agents. Herein, a method is presented that uses DNA microarray expression profiling of large sets of normal and cancer tissues to identify targets expressed in cancer but not expressed in relevant normal tissues. Identified targets are subsequently validated for protein expression using tissue microarray. Further validations are performed by quantifying expression in pancreatic cancer cells by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), by immunocytochemistry and immunohistochemistry, and by reviewing data and literature in public databases. Validated targets are selected for ligand development based on the existence of a known ligand or by known structure-activity relationships useful for development of novel ligands.
Morse
David L
DL
Molecular and Functional Imaging, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Hostetter
Galen
G
Balagurunathan
Yoganand
Y
Gillies
Robert J
RJ
Han
Haiyong
H
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D030541:Databases, Genetic; D016503:Drug Delivery Systems / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000302:isolation & purification; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D008024:Ligands; D012334:RNA, Neoplasm