Abstract C291: Targeting SDF-1 (CXCL12) pathway to inhibit the recurrence of breast cancer brain metastases after whole-brain irradiation.

Abstract The presence of tumor-associated macrophages (TAMs) in tumors strongly correlates with poor outcome. At least one lineage of TAMs originates from the peripheral bone marrow-derived mononuclear cells. We have previously reported that bone marrow-derived CD11b+ myeloid cells contribute to tumor regrowth after irradiation by homing to the irradiated site, where they aid in restoring tumor vasculature. We have also shown that inhibiting the recruitment of CD11b+ monocytes/macrophages by blocking the SDF-1 (CXCL12)-CXCR4 axis prevents or delays recurrence of mouse and rat glioblastoma after irradiation. We further demonstrate that TAMs in the irradiated glioblastoma could be detected in vivo by magnetic resonance (MR) imaging of iron oxide nanoparticles phagocytosed by TAMs. Radiation remains one of the major modalities for treatment of breast cancer brain metastases (BCBMs). We hypothesized that inhibition of SDF-1 mediated neovasculogenesis may be as useful for treatment of BCBMs as it is for treatment of glioblastoma. In this study, brain metastases from MDA-MB-231-BR3 cells injected through intra-carotid artery in nude mice were detected by bioluminescence imaging. SDF-1 activity was inhibited using Spiegelmer NOX-A12. Treatment with NOX-A12 began immediately after irradiation, and continued every second day until the end of the experiment. We show that combination of NOX-A12 with 12Gy resulted in marked delay of metastatic regrowth after irradiation compared to 12Gy alone and a doubling of the survival time of the mice. Detection of TAMs using MR imaging of iron oxide nanoparticles is under way. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C291. Citation Format: Sophia Chernikova, G-One Ahn, Shie-Chau Liu, Jason Stafford, J. Martin Brown. Targeting SDF-1 (CXCL12) pathway to inhibit the recurrence of breast cancer brain metastases after whole-brain irradiation. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C291.