Related Experiment Video
Updated: Jan 10, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Therapeutic potential of TAS-115 in 3D breast cancer models
Sendegul Yildirim1,2,3, Momoka T Nagamine1,2, Myoung Hwan Kim1,2
1The Huck Institutes of Life Sciences, Penn State University, University Park, PA 16802, United States of America.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. TAS-115, a multi-receptor tyrosine kinase inhibitor, has not previously been evaluated in TNBC. Here, we investigated its therapeutic effects alone and in combination with doxorubicin (DOXO), using three-dimensional heterotypic spheroid models, including free-standing, bioprinted static, and perfused systems. TAS-115 significantly reduced cell proliferation and viability, enhanced apoptosis, and suppressed c-mesenchymal-epithelial transition/hepatocyte growth factor and PI3K/Akt/mTOR signaling. Combined treatment with DOXO further amplified these effects. In perfused bioprinted models, TAS-115 markedly inhibited tumor cell migration, highlighting its potential to limit metastatic behavior. These findings identify TAS-115 as a promising therapeutic strategy for TNBC, either as a monotherapy or in combination with chemotherapy.
Insights
TAS-115, a novel tyrosine kinase inhibitor, shows promise for treating triple-negative breast cancer (TNBC). It effectively reduced tumor growth and migration, especially when combined with doxorubicin (DOXO).
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Triple-negative breast cancer (TNBC) is aggressive with few treatment options.
- TAS-115, a multi-receptor tyrosine kinase inhibitor, is a potential new therapy.
- Its efficacy in TNBC has not been previously studied.
Purpose of the Study:
- To investigate the therapeutic effects of TAS-115 in triple-negative breast cancer (TNBC).
- To evaluate TAS-115 as a monotherapy and in combination with doxorubicin (DOXO).
- To assess TAS-115's impact on TNBC cell signaling and metastatic potential.
Main Methods:
- Utilized three-dimensional heterotypic spheroid models: free-standing, static bioprinted, and perfused bioprinted systems.
- Assessed TAS-115's effects on cell proliferation, viability, apoptosis, and key signaling pathways (c-MET/HGF, PI3K/Akt/mTOR).
- Evaluated the combined effects of TAS-115 and DOXO, including tumor cell migration in perfused models.
Main Results:
- TAS-115 significantly reduced TNBC cell proliferation, viability, and enhanced apoptosis.
- It suppressed c-mesenchymal-epithelial transition/hepatocyte growth factor and PI3K/Akt/mTOR signaling pathways.
- Combined TAS-115 and DOXO treatment amplified these anti-cancer effects. TAS-115 inhibited tumor cell migration in perfused models.
Conclusions:
- TAS-115 demonstrates significant therapeutic potential as a monotherapy for triple-negative breast cancer (TNBC).
- Combination therapy with doxorubicin (DOXO) further enhances TAS-115's efficacy.
- TAS-115 shows promise in inhibiting TNBC metastasis, suggesting a valuable new treatment strategy.
