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Updated: Mar 20, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer
Meenakshi Upreti1,2, Amar Jyoti1,2, Sara E Johnson3
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
Abstract:
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.
Insights
Targeting tumor-associated endothelium offers a novel strategy for Triple Negative Breast Cancer (TNBC) treatment. This study demonstrates a nanotherapeutic approach combining radiation and targeted liposomes effectively inhibits TNBC growth and metastasis.
Area of Science:
- Oncology
- Nanomedicine
- Cancer Biology
Background:
- Triple Negative Breast Cancer (TNBC) lacks FDA-approved targeted therapies.
- Current TNBC trials focus on epithelial cancer cells, overlooking tumor-associated endothelium.
- Elevated stromal galectin-1 is observed in TNBC clinical samples.
Purpose of the Study:
- To explore targeted delivery of cytotoxic payloads to tumor-associated endothelium as a novel therapeutic strategy for TNBC.
- To investigate the efficacy of anginex-conjugated arsenic-cisplatin loaded liposomes targeting radiation-induced stromal galectin-1.
- To evaluate a multimodal nanotherapeutic strategy in a murine TNBC model.
Main Methods:
- Utilized a novel murine TNBC model with orthotopic tumors derived from 3D tumor tissue analogs (TTA).
- Developed anginex-conjugated arsenic-cisplatin loaded liposomes for targeted delivery.
- Administered a combined treatment regimen of radiation and targeted liposomes.
Main Results:
- Demonstrated significant inhibition of tumor growth and metastasis in the TNBC model.
- The combined treatment regimen was well-tolerated.
- Showcased enhanced chemotherapy delivery via receptor-mediated targeting concurrent with clinically relevant radiation doses, while limiting toxicity.
Conclusions:
- Targeted delivery to tumor-associated endothelium represents a promising, unexplored therapeutic avenue for TNBC.
- The multimodal nanotherapeutic strategy effectively targets the TNBC microenvironment.
- This approach offers a means to enhance chemotherapy delivery and limit toxicity in TNBC treatment.
