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Open Access 01-12-2024 | Breast Cancer | Research

Targeting tumor–stromal interactions in triple-negative breast cancer using a human vascularized micro-tumor model

Authors: Stephanie J. Hachey, Christopher J. Hatch, Daniela Gaebler, Aneela Mocherla, Kevin Nee, Kai Kessenbrock, Christopher C. W. Hughes

Published in: Breast Cancer Research | Issue 1/2024

Abstract

Triple-negative breast cancer (TNBC) is highly aggressive with limited available treatments. Stromal cells in the tumor microenvironment (TME) are crucial in TNBC progression; however, understanding the molecular basis of stromal cell activation and tumor–stromal crosstalk in TNBC is limited. To investigate therapeutic targets in the TNBC stromal niche, we used an advanced human in vitro microphysiological system called the vascularized micro-tumor (VMT). Using single-cell RNA sequencing, we revealed that normal breast tissue stromal cells activate neoplastic signaling pathways in the TNBC TME. By comparing interactions in VMTs with clinical data, we identified therapeutic targets at the tumor–stromal interface with potential clinical significance. Combining treatments targeting Tie2 signaling with paclitaxel resulted in vessel normalization and increased efficacy of paclitaxel in the TNBC VMT. Dual inhibition of HER3 and Akt also showed efficacy against TNBC. These data demonstrate the potential of inducing a favorable TME as a targeted therapeutic approach in TNBC.

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Title: Targeting tumor–stromal interactions in triple-negative breast cancer using a human vascularized micro-tumor model
Authors: Stephanie J. Hachey
Christopher J. Hatch
Daniela Gaebler
Aneela Mocherla
Kevin Nee
Kai Kessenbrock
Christopher C. W. Hughes
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research / Issue 1/2024
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-023-01760-y

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