Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment.

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Notes/Citation Information

Published in Oncotarget, v. 7, no. 27, p. 41559-41574.

Licensed under a Creative Commons Attribution 3.0 License.

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Funding Information

This research was supported by National Cancer Institute grants R21CA173609 to M.U, R25CA153954 (CNTC, UK) and Cancer Nanotechnology Platform Partnership U01CA151461 to T.V.O. We also acknowledge support from the Markey Cancer Center shared resource facilities (NCI grant P30 CA177558) and the NU Quantitative Bio-elemental Imaging Center (QBIC) supported by NASA Ames Research Center NNA06CB93G for performing the metal analysis in this study.

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Supplementary Materials: Figure S1-S4