Imaging CXCL12-CXCR4 Signaling and Inhibition in Ovarian Cancer
Abstract
CXCR4 and its chemokine ligand CXCL12 are potential targets for molecular therapy of ovarian cancer. Receptor CXCR4 is expressed by ovarian cancer cells in approximately 50% of patients. High levels of CXCL12 are present in ascites of patients with ovarian cancer, providing a local source of chemokine ligand in the tumor microenvironment. CXCL12 signaling through CXCR4 activates pathways that could promote tumor growth, invasion, metastasis, and resistance to chemotherapy. To advance clinical translation of CXCR4 inhibitors for therapy of ovarian cancer, we developed molecular imaging reporters for CXCR4 signaling that can be used for cell-based assays and real-time imaging studies in mouse xenograft models of ovarian cancer. After validating that these reporters correspond with biochemical measures of CXCL12-CXCR4 signaling, we used optical imaging to quantify pharmacodynamics of therapy for CXCR4 targeted inhibitors in mice with ovarian cancer. Treatment studies established that inhibiting CXCR4 prolonged survival of mice with ovarian cancer and potentially could improve treatment efficacy of a standard chemotherapeutic drug, cisplatin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA593931
Entities
People
- Gary Luker
Organizations
- University of Michigan