Project Details
Description
Original Project Abstract
Recently, the incidence of esophageal (EAC) and gastro-esophageal junction (GEJAC)
adenocarcinoma has increased dramatically, and have a poor 5-year survival rate of less than
15%. When detected early, these patients can have a good clinical outcome following surgery.
These observations underscore the importance of early cancer detection. Patients with
Barrett’s esophagus (BE) are known to be at increased risk.
Our overarching goal is to advance new methods of imaging to visualize the effects of spatial
distribution of genetic alterations in BE by using novel imaging methods to evaluate tumor
heterogeneity on the progression toward EAC. We propose a multi-institutional, trans-
disciplinary, translational Research Center in the Barrett’s Esophagus Translational Research
Network (BETRNet). Our mission is to build on our expertise in genomic characterization,
peptide biochemistry, and clinical translation to achieve our ultimate goal to perform early
cancer detection at an early stage where therapeutic intervention can be most effective. We
will identify a complementary panel of genes that are overexpressed on the cell surface and will
be used to develop and validate new peptide imaging agents. The targets chosen will address 3
important clinical needs: 1) Real-time endoscopic identification of pre-malignant lesions and
early stage cancer to guide endoscopic resection; 2) Risk stratification of BE patients for timing
of endoscopic surveillance; and 3) Detection of gastro-esophageal junction adenocarcinomas in
patients without endoscopic appearance of BE.
We will use state-of-the-art genomic tools to to identify early overexpressed gene targets that
arise in progression of BE to EAC by providing comprehensive analyses of gene expression
alterations, DNA copy number variation, and genetic mutations. We will select candidate genes
that are expressed on the cell surface where they can be endoscopically imaged in vivo. We will
rigorously validate the panel of candidate targets with quantitative RT-PCR and
immunohistochemistry on tissue microarrays using an independent cohort of human esophagus
specimens. We will use these targets to first identify and validate monomer peptides that are
highly specific. We will then arrange monomer peptides in a dimer configuration to produce
multivalent ligand target interactions to improve binding performance and allow for early
targets to be detected at low levels of expression. We will use a flexible fiber multi-spectral
endoscope that can pass through the working channel of a standard medical endoscope to
detect multiple targets at the same time.
Successful completion of these aims will provide an integrated multi-spectral imaging
methodology to longitudinally visualize overexpressed molecular targets that drive progression
of Barrett’s esophagus to esophageal adenocarcinoma. This innovative approach can serve as
the foundation for validated preventive measures to improve patient management.
Status | Finished |
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Effective start/end date | 9/21/11 → 4/23/23 |
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